NAMPT inhibitors

ABSTRACT

Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed.

This application claims priority to U.S. Provisional Application Ser.No. 61/645,685, filed May 11, 2012, U.S. Provisional Application Ser.No. 61/719,008, filed Oct. 26, 2012, and U.S. Provisional ApplicationSer. No. 61/779,702, filed May 13, 2013 which are incorporated byreference in their entirety.

FIELD OF THE INVENTION

This invention pertains to compounds which inhibit the activity ofNAMPT, compositions containing the compounds, and methods of treatingdiseases during which NAMPT is expressed.

BACKGROUND OF THE INVENTION

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays acritical role in many physiologically essential processes (Ziegkel, M.Eur. J. Biochem. 267, 1550-1564, 2000). NAD is necessary for severalsignaling pathways including among others poly ADP-ribosylation in DNArepair, mono-ADP-ribosylation in both the immune system andG-protein-coupled signaling, and NAD is also required by sirtuins fortheir deacetylase activity (Garten, A. et al Trends in Endocrinology andMetabolism, 20, 130-138, 2008).

NAMPT (also known as pre-B-cell-colony-enhancing factor (PBEF) andvisfatin) is an enzyme that catalyzes the phosphoribosylation ofnicotinamide and is the rate-limiting enzyme in one of two pathways thatsalvage NAD.

Increasing evidence suggests that NAMPT inhibitors have potential asanticancer agents. Cancer cells have a higher basal turnover of NAD andalso display higher energy requirements compared with normal cells.Additionally, increased NAMPT expression has been reported in colorectalcancer (Van Beijnum, J. R. et al Int. J. Cancer 101, 118-127, 2002) andNAMPT is involved in angiogenesis (Kim, S. R. et al. Biochem. Biophys.Res. Commun. 357, 150-156, 2007). Small-molecule inhibitors of NAMPThave been shown to cause depletion of intracellular NAD+ levels andultimately induce tumor cell death (Hansen, C M et al. Anticancer Res.20, 42111-4220, 2000) as well as inhibit tumor growth in xenograftmodels (Olese, U. H. et al. Mol Cancer Ther. 9, 1609-1617, 2010).

NAMPT inhibitors also have potential as therapeutic agents ininflammatory and metabolic disorders (Galli, M. et al Cancer Res. 70,8-11, 2010). For example, NAMPT is the predominant enzyme in T and Blymphocytes. Selective inhibition of NAMPT leads to NAD+ depletion inlymphocytes blocking the expansion that accompanies autoimmune diseaseprogression whereas cell types expressing the other NAD+ generatingpathways might be spared. A small molecule NAMPT inhibitor (FK866) hasbeen shown to selectively block proliferation and induce apoptosis ofactivated T cells and was efficacious in animal models of arthritis(collagen induced arthritis) (Busso, N. et al. Plos One 3, e2267, 2008).FK866 ameliorated the manifestations of experimental autoimmuneencephalomyelitis (EAE), a model of T-cell mediated autoimmunedisorders. (Bruzzone, Set al. Plos One 4, e7897, 2009). NaMPT activityincreases NF-kB transcriptional activity in human vascular endothelialcell, resulting in MMP-2 and MMP-9 activation, suggesting a role forNAMPT inhibitors in the prevention of inflammatory mediatedcomplications of obesity and type 2 diabetes (Adya, R. et. Al. DiabetesCare, 31, 758-760, 2008).

SUMMARY OF THE INVENTION

One embodiment of this invention, therefore, pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (IA)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl,hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl,C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl; wherein each R²C₄-C₆-alkyl, C₄-C₆-alkenyl,and C₄-C₆-alkynyl is substituted with one or more substituentsindependently selected from the group consisting of R³, OR³, SR³,S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂,NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³,NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂,C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³,C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR³, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R² aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴,N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴,NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴,NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴,C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R³, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl,and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵,C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵,NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂,NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵,C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂,SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl,cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substitutedwith one or more substituents independently selected from the groupconsisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶,OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶,NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶,NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶,C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸,N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸,NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸,OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹,N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹,NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹,OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁶SO₂R¹⁶, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹,C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹,NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹,NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂,C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹,C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Brand I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenylis optionally substituted with one or more substituents independentlyselected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹²,C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and

R¹², at each occurrence, is independently selected alkyl.

In one embodiment of Formula (IA), X¹ is CR¹ and X² is CR¹. In anotherembodiment of Formula (IA), R¹, at each occurrence, is hydrogen. Inanother embodiment of Formula (IA), X¹ is CR¹ and X² is CR¹, and R¹, ateach occurrence, is hydrogen. In another embodiment of Formula (IA), Y¹is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl.In another embodiment of Formula (IA), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;and R² is phenyl; wherein each R² phenyl is substituted with one OR⁴. Inanother embodiment of Formula (IA), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;and R² is phenyl; wherein each R² phenyl is substituted with one R⁴. Inanother embodiment of Formula (IA), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;R² is phenyl; wherein each R² phenyl is substituted with one OR⁴, and,R⁴, at each occurrence, is heterocyclyl. In another embodiment ofFormula (IA), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;R² is phenyl; wherein each R² phenyl is substituted with one R⁴, and,R⁴, at each occurrence, is heterocyclyl.

Still another embodiment pertains to compounds, which are

-   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(5-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)    phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(6-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydro    furan-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   methyl 4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)benzoate;-   N-(4-cyanophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)butyl]piperidine-1-carboxylate;-   N-{4-[1-(2,2-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(methylsulfanyl)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(methylsulfanyl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydro    furan-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydro    furan-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[3-(pyrrolidin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]pyrrolidine-1-carboxylate;-   tert-butyl    (3R)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    (3S)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]azetidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]azetidine-1-carboxylate;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydro    furan-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydro    furan-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro    furan-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(2-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   tert-butyl    4-[4-({[3-(4-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   N-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(2-fluoropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-propanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(morpholin-4-ylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(4-methylpiperazin-1-yl)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(N,N-dimethyl-beta-alanyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(pyrrolidin-1-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(2-fluoropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(4-chloropyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(2-chloropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   4-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)piperazine-1-carboxamide;-   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-cyclopropylethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(5-oxo-L-prolyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-oxopropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-pentanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(bicyclo[2.2.1]hept-2-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-D-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-L-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(4-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N-acetyl-L-leucyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-propanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}-phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(ethoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-acetylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;    and pharmaceutically acceptable salts thereof.

Another embodiment pertains to a composition for treating inflammatoryand tissue repair disorders; particularly rheumatoid arthritis,inflammatory bowel disease, asthma and COPD (chronic obstructivepulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases;dermatosis, including psoriasis, atopic dermatitis and ultra-violetinduced skin damage; autoimmune diseases including systemic upuserythematosis, multiple sclerosis, psoriatic arthritis, ankylosingspondylitis, tissue and organ rejection, Alzheimer's disease, stroke,athersclerosis, restenosis, diabetes, glomerulonephritis, cancer,particularly wherein the cancer is selected from breast, prostate, lung,colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphomaor Hodgkin's disease, cachexia, inflammation associated with infectionand certain viral infections, including Acquired Immune DeficiencySyndrome (AIDS), adult respiratory distress syndrome, and ataxiatelengiectasia, said composition comprising an excipient and atherapeutically effective amount of a compound of Formula (IA), orpharmaceutically acceptable salts thereof.

Another embodiment pertains to a method of treating inflammatory andtissue repair disorders; particularly rheumatoid arthritis, inflammatorybowel disease, asthma and COPD (chronic obstructive pulmonary disease),osteoarthritis, osteoporosis and fibrotic diseases; dermatosis,including psoriasis, atopic dermatitis and ultra-violet induced skindamage; autoimmune diseases including systemic lupus erythematosis,multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissueand organ rejection, Alzheimer's disease, stroke, athersclerosis,restenosis, diabetes, glomerulonephritis, cancer, particularly whereinthe cancer is selected from breast, prostate, lung, colon, cervix,ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin'sdisease, cachexia, inflammation associated with infection and certainviral infections, including Acquired Immune Deficiency Syndrome (AIDS),adult respiratory distress syndrome, and ataxia telengiectasia in apatient, said method comprising administering to the patient atherapeutically effective amount of a compound of Formula (IA), orpharmaceutically acceptable salts thereof.

Another embodiment pertains to a method of treating inflammatory andtissue repair disorders; particularly rheumatoid arthritis, inflammatorybowel disease, asthma and COPD (chronic obstructive pulmonary disease),osteoarthritis, osteoporosis and fibrotic diseases; dermatosis,including psoriasis, atopic dermatitis and ultra-violet induced skindamage; autoimmune diseases including systemic lupus erythematosis,multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissueand organ rejection, Alzheimer's disease, stroke, athersclerosis,restenosis, diabetes, glomerulonephritis, cancer, particularly whereinthe cancer is selected from breast, prostate, lung, colon, cervix,ovary, skin, CNS, bladder, pancreas, leukemia, lymphoma or Hodgkin'sdisease, cachexia, inflammation associated with infection and certainviral infections, including Acquired Immune Deficiency Syndrome (AIDS),adult respiratory distress syndrome, and ataxia telengiectasia or spleencancer in a patient, said method comprising administering to the patienttherapeutically effective amount of the compound of Formula (IA), orpharmaceutically acceptable salts thereof; and a therapeuticallyeffective amount of one additional therapeutic agent or more than oneadditional therapeutic agent.

DETAILED DESCRIPTION OF THE INVENTION

This detailed description is intended only to acquaint others skilled inthe art with Applicants' invention, its principles, and its practicalapplication so that others skilled in the art may adapt and apply theinvention in its numerous forms, as they may be best suited to therequirements of a particular use. This description and its specificexamples are intended for purposes of illustration only. This invention,therefore, is not limited to the embodiments described in this patentapplication, and may be variously modified.

Abbreviations and Definitions

Unless otherwise defined herein, scientific and technical terms used inconnection with the present invention shall have the meanings that arecommonly understood by those of ordinary skill in the art. The meaningand scope of the terms should be clear, however, in the event of anylatent ambiguity, definitions provided herein take precedent over anydictionary or extrinsic definition. In this application, the use of “or”means “and/or” unless stated otherwise. Furthermore, the use of the term“including”, as well as other forms, such as “includes” and “included”,is not limiting. With reference to the use of the words “comprise” or“comprises” or “comprising” in this patent application (including theclaims), Applicants note that unless the context requires otherwise,those words are used on the basis and clear understanding that they areto be interpreted inclusively, rather than exclusively, and thatApplicants intend each of those words to be so interpreted in construingthis patent application, including the claims below. For a variable thatoccurs more than one time in any substituent or in the compound of theinvention or any other formulae herein, its definition on eachoccurrence is independent of its definition at every other occurrence.Combinations of substituents are permissible only if such combinationsresult in stable compounds. Stable compounds are compounds which can beisolated in a useful degree of purity from a reaction mixture.

It is meant to be understood that proper valences are maintained for allcombinations herein, that monovalent moieties having more than one atomare attached through their left ends, and that divalent moieties aredrawn from left to right.

As used in the specification and the appended claims, unless specifiedto the contrary, the following terms have the meaning indicated:

The term “alkyl” (alone or in combination with another term(s)) means astraight- or branched-chain saturated hydrocarbyl substituent typicallycontaining from 1 to about 10 carbon atoms; or in another embodiment,from 1 to about 8 carbon atoms; in another embodiment, from 1 to about 6carbon atoms; and in another embodiment, from 1 to about 4 carbon atoms.Examples of such substituents include methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl,and hexyl and the like.

The term “alkenyl” (alone or in combination with another term(s)) meansa straight- or branched-chain hydrocarbyl substituent containing one ormore double bonds and typically from 2 to about 10 carbon atoms; or inanother embodiment, from 2 to about 8 carbon atoms; in anotherembodiment, from 2 to about 6 carbon atoms; and in another embodiment,from 2 to about 4 carbon atoms. Examples of such substituents includeethenyl (vinyl), 2-propenyl, 3-propenyl, 1,4-pentadienyl,1,4-butadienyl, 1-butenyl, 2-butenyl, and 3-butenyl and the like.

The term “alkynyl” (alone or in combination with another term(s)) meansa straight- or branched-chain hydrocarbyl substituent containing one ormore triple bonds and typically from 2 to about 10 carbon atoms; or inanother embodiment, from 2 to about 8 carbon atoms; in anotherembodiment, from 2 to about 6 carbon atoms; and in another embodiment,from 2 to about 4 carbon atoms. Examples of such substituents includeethynyl, 2-propynyl, 3-propynyl, 2-butynyl, and 3-butynyl and the like.

The term “carbocyclyl” (alone or in combination with another term(s))means a saturated cyclic (i.e., “cycloalkyl”), partially saturatedcyclic (i.e., “cycloalkenyl”), or completely unsaturated (i.e., “aryl”)hydrocarbyl substituent containing from 3 to 14 carbon ring atoms (“ringatoms” are the atoms bound together to form the ring or rings of acyclic substituent). A carbocyclyl may be a single-ring (monocyclic) orpolycyclic ring structure.

A carbocyclyl may be a single ring structure, which typically containsfrom 3 to 8 ring atoms, more typically from 3 to 6 ring atoms, and evenmore typically 5 to 6 ring atoms. Examples of such single-ringcarbocyclyls include cyclopropyl (cyclopropanyl), cyclobutyl(cyclobutanyl), cyclopentyl (cyclopentanyl), cyclopentenyl,cyclopentadienyl, cyclohexyl (cyclohexanyl), cyclohexenyl,cyclohexadienyl, and phenyl. A carbocyclyl may alternatively bepolycyclic (i.e., may contain more than one ring). Examples ofpolycyclic carbocyclyls include bridged, fused, and spirocycliccarbocyclyls. In a spirocyclic carbocyclyl, one atom is common to twodifferent rings. An example of a spirocyclic carbocyclyl isspiropentanyl. In a bridged carbocyclyl, the rings share at least twocommon non-adjacent atoms. Examples of bridged carbocyclyls includebicyclo[2.2.1]heptanyl, bicyclo[2.2.1]hept-2-enyl, and adamantanyl. In afused-ring carbocyclyl system, two or more rings may be fused together,such that two rings share one common bond. Examples of two- orthree-fused ring carbocyclyls include naphthalenyl,tetrahydronaphthalenyl (tetralinyl), indenyl, indanyl (dihydroindenyl),anthracenyl, phenanthrenyl, and decalinyl.

The term “cycloalkyl” (alone or in combination with another term(s))means a saturated cyclic hydrocarbyl substituent containing from 3 to 14carbon ring atoms. A cycloalkyl may be a single carbon ring, whichtypically contains from 3 to 8 carbon ring atoms and more typically from3 to 6 ring atoms. Examples of single-ring cycloalkyls includecyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. A cycloalkyl mayalternatively be polycyclic or contain more than one ring. Examples ofpolycyclic cycloalkyls include bridged, fused, and spirocycliccarbocyclyls.

The term “aryl” (alone or in combination with another term(s)) means anaromatic carbocyclyl containing from 6 to 14 carbon ring atoms. An arylmay be monocyclic or polycyclic (i.e., may contain more than one ring).In the case of polycyclic aromatic rings, only one ring the polycyclicsystem is required to be unsaturated while the remaining ring(s) may besaturated, partially saturated or unsaturated. Examples of aryls includephenyl, naphthalenyl, indenyl, indanyl, and tetrahydronapthyl.

In some instances, the number of carbon atoms in a hydrocarbylsubstituent (e.g., alkyl, alkenyl, alkynyl, or cycloalkyl) is indicatedby the prefix “C_(x)-C_(y)-”, wherein x is the minimum and y is themaximum number of carbon atoms in the substituent. Thus, for example,“C₁-C₆-alkyl” refers to an alkyl substituent containing from 1 to 6carbon atoms. Illustrating further, C₃-C₈-cycloalkyl means a saturatedhydrocarbyl ring containing from 3 to 8 carbon ring atoms.

The term “hydrogen” (alone or in combination with another term(s)) meansa hydrogen radical, and may be depicted as —H.

The term “hydroxy” (alone or in combination with another term(s)) means—OH.

The term “carboxy” (alone or in combination with another term(s)) means—C(O)—OH.

The term “amino” (alone or in combination with another term(s)) means—NH₂.

The term “halogen” or “halo” (alone or in combination with anotherterm(s)) means a fluorine radical (which may be depicted as —F),chlorine radical (which may be depicted as —Cl), bromine radical (whichmay be depicted as —Br), or iodine radical (which may be depicted as—I).

If a substituent is described as being “substituted”, a non-hydrogenradical is in the place of hydrogen radical on a carbon or nitrogen ofthe substituent. Thus, for example, a substituted alkyl substituent isan alkyl substituent in which at least one non-hydrogen radical is inthe place of a hydrogen radical on the alkyl substituent. To illustrate,monofluoroalkyl is alkyl substituted with a fluoro radical, anddifluoroalkyl is alkyl substituted with two fluoro radicals. It shouldbe recognized that if there are more than one substitution on asubstituent, each non-hydrogen radical may be identical or different(unless otherwise stated).

If a substituent is described as being “optionally substituted”, thesubstituent may be either (1) not substituted or (2) substituted. If asubstituent is described as being optionally substituted with up to aparticular number of non-hydrogen radicals, that substituent may beeither (1) not substituted; or (2) substituted by up to that particularnumber of non-hydrogen radicals or by up to the maximum number ofsubstitutable positions on the substituent, whichever is less. Thus, forexample, if a substituent is described as a heteroaryl optionallysubstituted with up to 3 non-hydrogen radicals, then any heteroaryl withless than 3 substitutable positions would be optionally substituted byup to only as many non-hydrogen radicals as the heteroaryl hassubstitutable positions. To illustrate, tetrazolyl (which has only onesubstitutable position) would be optionally substituted with up to onenon-hydrogen radical. To illustrate further, if an amino nitrogen isdescribed as being optionally substituted with up to 2 non-hydrogenradicals, then a primary amino nitrogen will be optionally substitutedwith up to 2 non-hydrogen radicals, whereas a secondary amino nitrogenwill be optionally substituted with up to only 1 non-hydrogen radical.If a substituent is described as being optionally substituted with oneor more non-hydrogen radicals, that substituent may be either (1) notsubstituted; or (2) substituted by up to the maximum number ofsubstitutable positions on the substituent. Thus, for example, if asubstituent is described as a heteroaryl optionally substituted with oneor more non-hydrogen radicals, then any heteroaryl with 3 substitutablepositions would be optionally substituted by one, two or threenon-hydrogen radicals. To illustrate, tetrazolyl (which has only onesubstitutable position) would be optionally substituted with up to onenon-hydrogen radical.

This patent application uses the terms “substituent” and “radical”interchangeably.

The prefix “halo” indicates that the substituent to which the prefix isattached is substituted with one or more independently selected halogenradicals. For example, haloalkyl means an alkyl substituent in which atleast one hydrogen radical is replaced with a halogen radical. Examplesof haloalkyls include chloromethyl, 1-bromoethyl, fluoromethyl,difluoromethyl, trifluoromethyl, and 1,1,1-trifluoroethyl. It should berecognized that if a substituent is substituted by more than one halogenradical, those halogen radicals may be identical or different (unlessotherwise stated).

The prefix “perhalo” indicates that every hydrogen radical on thesubstituent to which the prefix is attached is replaced withindependently selected halogen radicals, i.e., each hydrogen radical onthe substituent is replaced with a halogen radical. If all the halogenradicals are identical, the prefix typically will identify the halogenradical. Thus, for example, the term “perfluoro” means that everyhydrogen radical on the substituent to which the prefix is attached issubstituted with a fluorine radical. To illustrate, the term“perfluoroalkyl” means an alkyl substituent wherein a fluorine radicalis in the place of each hydrogen radical.

The term “carbonyl” (alone or in combination with another term(s)) means—C(O)—.

The term “aminocarbonyl” (alone or in combination with another term(s))means —C(O)—NH₂.

The term “oxo” (alone or in combination with another term(s)) means(═O).

The term “oxy” (alone or in combination with another term(s)) means anether substituent, and may be depicted as —O—.

The term “alkylhydroxy” (alone or in combination with another term(s))means -alkyl-OH.

The term “alkylamino” (alone or in combination with another term(s))means -alkyl-NH₂.

The term “alkyloxy” (alone or in combination with another term(s)) meansan alkylether substituent, i.e., —O-alkyl. Examples of such asubstituent include methoxy (—O—CH₃), ethoxy, n-propoxy, isopropoxy,n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy.

The term “alkylcarbonyl” (alone or in combination with another term(s))means —C(O)-alkyl.

The term “aminoalkylcarbonyl” (alone or in combination with anotherterm(s)) means —C(O)-alkyl-NH₂.

The term “alkyloxycarbonyl” (alone or in combination with anotherterm(s)) means —C(O)—O-alkyl.

The term “carbocyclylcarbonyl” (alone or in combination with anotherterm(s)) means —C(O)-carbocyclyl.

Similarly, the term “heterocyclylcarbonyl” (alone or in combination withanother term(s)) means —C(O)-heterocyclyl.

The term “carbocyclylalkylcarbonyl” (alone or in combination withanother term(s)) means —C(O)-alkyl-carbocyclyl.

Similarly, the term “heterocyclylalkylcarbonyl” (alone or in combinationwith another term(s)) means —C(O)-alkyl-heterocyclyl.

The term “carbocyclyloxycarbonyl” (alone or in combination with anotherterm(s)) means —C(O)—O-carbocyclyl.

The term “carbocyclylalkyloxycarbonyl” (alone or in combination withanother term(s)) means —C(O)—O-alkyl-carbocyclyl.

The term “thio” or “thia” (alone or in combination with another term(s))means a thiaether substituent, i.e., an ether substituent wherein adivalent sulfur atom is in the place of the ether oxygen atom. Such asubstituent may be depicted as —S—. This, for example,“alkyl-thio-alkyl” means alkyl-5-alkyl (alkyl-sulfanyl-alkyl).

The term “thiol” or “sulfhydryl” (alone or in combination with anotherterm(s)) means a sulfhydryl substituent, and may be depicted as —SH. Theterm “(thiocarbonyl)” (alone or in combination with another term(s))means a carbonyl wherein the oxygen atom has been replaced with asulfur. Such a substituent may be depicted as —C(S)—.

The term “sulfonyl” (alone or in combination with another term(s)) means—S(O)₂—.

The term “aminosulfonyl” (alone or in combination with another term(s))means —S(O)₂—NH₂.

The term “sulfinyl” or “sulfoxido” (alone or in combination with anotherterm(s)) means —S(O)—.

The term “heterocyclyl” (alone or in combination with another term(s))means a saturated (i.e., “heterocycloalkyl”), partially saturated (i.e.,“heterocycloalkenyl”), or completely unsaturated (i.e., “heteroaryl”)ring structure containing a total of 3 to 14 ring atoms. At least one ofthe ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), withthe remaining ring atoms being independently selected from the groupconsisting of carbon, oxygen, nitrogen, and sulfur. A heterocyclyl maybe a single-ring (monocyclic) or polycyclic ring structure.

A heterocyclyl may be a single ring, which typically contains from 3 to7 ring atoms, more typically from 3 to 6 ring atoms, and even moretypically 5 to 6 ring atoms. Examples of single-ring heterocyclylsinclude 1,2,3,6-tetrahydropyridine, thiomorpholinyl, tetrahydropyranyl,furanyl, dihydrofuranyl, tetrahydrofuranyl, thiophenyl (thiofuranyl),dihydrothiophenyl, tetrahydrothiophenyl, pyrrolyl, pyrrolinyl,pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl,pyrazolinyl, pyrazolidinyl, triazolyl, tetrazolyl, oxazolyl,oxazolidinyl, isoxazolidinyl, isoxazolyl, thiazolyl, isothiazolyl,thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazolidinyl,thiodiazolyl, oxadiazolyl (including 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl(furazanyl), or 1,3,4-oxadiazolyl),oxatriazolyl (including 1,2,3,4-oxatriazolyl or 1,2,3,5-oxatriazolyl),dioxazolyl (including 1,2,3-dioxazolyl, 1,2,4-dioxazolyl,1,3,2-dioxazolyl, or 1,3,4-dioxazolyl), oxathiazolyl, oxathiolyl,oxathiolanyl, pyranyl, dihydropyranyl, thiopyranyl,tetrahydrothiopyranyl, pyridinyl (azinyl), piperidinyl, diazinyl(including pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), orpyrazinyl (1,4-diazinyl)), piperazinyl, pyrrolidin-2-only, triazinyl(including 1,3,5-triazinyl, 1,2,4-triazinyl, and 1,2,3-triazinyl)),oxazinyl (including 1,2-oxazinyl, 1,3-oxazinyl, or 1,4-oxazinyl)),oxathiazinyl (including 1,2,3-oxathiazinyl, 1,2,4-oxathiazinyl,1,2,5-oxathiazinyl, or 1,2,6-oxathiazinyl)), oxadiazinyl (including1,2,3-oxadiazinyl, 1,2,4-oxadiazinyl, 1,4,2-oxadiazinyl, or1,3,5-oxadiazinyl)), morpholinyl, azepinyl, oxepinyl, thiepinyl, anddiazepinyl.

A heterocyclyl may alternatively be polycyclic (i.e., may contain morethan one ring). Examples of polycyclic heterocyclyls include bridged,fused, and spirocyclic heterocyclyls. In a spirocyclic heterocyclyl, oneatom is common to two different rings. In a bridged heterocyclyl, therings share at least two common non-adjacent atoms. In a fused-ringheterocyclyl, two or more rings may be fused together, such that tworings share one common bond. Examples of fused-ring heterocyclylsinclude hexahydro-furo[3,4-c]pyrrole, hexahydro-furo[3,4-b]pyrrole,octahydro-pyrrolo[3,4-b]pyridine, octahydro-pyrrolo[3,4-c]pyridine,(3aR,6aR)-5-methyl-octahydro-pyrrolo[3,4-b]pyrrole,(3aR,6aR)-octahydro-pyrrolo[3,4-b]pyrrole,6-methyl-2,6-diaza-bicyclo[3.2.0]heptane,(3aS,6aR)-2-methyl-octahydro-pyrrolo[3,4-c]pyrrole,decahydro-[1,5]naphthyridine, 2,3-dihydrobenzofuranyl,2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indolyl, thieno[3,2-c]pyridinyl,furo[3,2-c]pyridinyl, phthalazin-1(2H)-onyl, isoquinolinyl,isoquinolin-1(2H)-onyl, 5,6,7,8-tetrahydrophthalazin-1(2H)-onyl,fluorophthalazin-1(2H)-onyl, (Z)-3H-benzo[d][1,2]diazepin-4(5H)-onyl,(trifluoromethyl)phthalazin-1(2H)-onyl,pyrrolo[1,2-d][1,2,4]triazin-1(2H)-onyl,1,2,3,4-tetrahydroisoquinolinyl, 2,3-dihydrobenzo[b][1,4]dioxinyl,5,6,7,8-tetrahydrophthalazin-1(2H)-onyl,5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl,5,6,7,8-tetrahydroimidazo[1,5-a]pyrazinyl, thieno[3,2-c]pyridinyl,furo[3,2-c]pyridinyl, indolizinyl, pyranopyrrolyl, 4H-quinolizinyl,purinyl, naphthyridinyl, pyridopyridinyl (includingpyrido[3,4-b]-pyridinyl, pyrido[3,2-b]-pyridinyl, orpyrido[4,3-b]-pyridinyl), and pteridinyl. Other examples of fused-ringheterocyclyls include benzo-fused heterocyclyls, such as benzimidazolyl,benzo[d][1,3]dioxolyl, indolyl, isoindolyl (isobenzazolyl,pseudoisoindolyl), indoleninyl (pseudoindolyl), isoindazolyl(benzpyrazolyl), benzazinyl (including quinolinyl (1-benzazinyl) orisoquinolinyl (2-benzazinyl)), phthalazinyl, quinoxalinyl, quinazolinyl,benzodiazinyl (including cinnolinyl (1,2-benzodiazinyl) or quinazolinyl(1,3-benzodiazinyl)), benzopyranyl (including chromanyl orisochromanyl), benzoxazinyl (including 1,3,2-benzoxazinyl,1,4,2-benzoxazinyl, 2,3,1-benzoxazinyl, or 3,1,4-benzoxazinyl), andbenzisoxazinyl (including 1,2-benzisoxazinyl or 1,4-benzisoxazinyl).Examples of spirocyclic heterocyclyls include1,4-dioxa-8-azaspiro[4.5]decanyl.

The term “3-12 membered heterocyclyl” (alone or in combination withanother term(s)) means a saturated (i.e., “heterocycloalkyl”), partiallysaturated (i.e., “heterocycloalkenyl”), or completely unsaturated (i.e.,“heteroaryl”) ring structure containing a total of 3 to 12 ring atoms.At least one of the ring atoms is a heteroatom (i.e., oxygen, nitrogen,or sulfur), with the remaining ring atoms being independently selectedfrom the group consisting of carbon, oxygen, nitrogen, and sulfur. A3-12 membered heterocyclyl may be a single-ring (monocyclic) orpolycyclic ring structure.

The term “heterocycloalkyl” (alone or in combination with anotherterm(s)) means a saturated heterocyclyl.

The term “heteroaryl” (alone or in combination with another term(s))means an aromatic heterocyclyl containing from 5 to 14 ring atoms. Aheteroaryl may be a single ring or 2 or 3 fused rings. Examples ofheteroaryl substituents include 6-membered ring substituents such aspyridyl, pyrazyl, pyrimidinyl, pyridazinyl, and 1,3,5-, 1,2,4- or1,2,3-triazinyl; 5-membered ring substituents such as imidazyl, furanyl,thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1,2,3-, 1,2,4-,1,2,5-, or 1,3,4-oxadiazolyl and isothiazolyl; 6/5-membered fused ringsubstituents such as benzothiofuranyl, benzisoxazolyl, benzoxazolyl, andpurinyl; and 6/6-membered fused rings such as benzopyranyl, quinolinyl,isoquinolinyl, cinnolinyl, quinazolinyl, and benzoxazinyl.

A prefix attached to a multi-component substituent only applies to thefirst component. To illustrate, the term “alkylcycloalkyl” contains twocomponents: alkyl and cycloalkyl. Thus, the C₁-C₆-prefix onC₁-C₆-alkylcycloalkyl means that the alkyl component of thealkylcycloalkyl contains from 1 to 6 carbon atoms; the C₁-C₆-prefix doesnot describe the cycloalkyl component. To illustrate further, the prefix“halo” on haloalkyloxyalkyl indicates that only the alkyloxy componentof the alkyloxyalkyl substituent is substituted with one or more halogenradicals. If halogen substitution may alternatively or additionallyoccur on the alkyl component, the substituent would instead be describedas “halogen-substituted alkyloxyalkyl” rather than “haloalkyloxyalkyl.”And finally, if the halogen substitution may only occur on the alkylcomponent, the substituent would instead be described as“alkyloxyhaloalkyl.”

The terms “treat”, “treating” and “treatment” refer to a method ofalleviating or abrogating a disease and/or its attendant symptoms.

The terms “prevent”, “preventing” and “prevention” refer to a method ofpreventing the onset of a disease and/or its attendant symptoms orbarring a subject from acquiring a disease. As used herein, “prevent”,“preventing” and “prevention” also include delaying the onset of adisease and/or its attendant symptoms and reducing a subject's risk ofacquiring a disease.

The term “therapeutically effective amount” refers to that amount of thecompound being administered sufficient to prevent development of oralleviate to some extent one or more of the symptoms of the condition ordisorder being treated.

The term “modulate” refers to the ability of a compound to increase ordecrease the function, or activity, of a kinase. “Modulation”, as usedherein in its various forms, is intended to encompass antagonism,agonism, partial antagonism and/or partial agonism of the activityassociated with kinase. Kinase inhibitors are compounds that, e.g., bindto, partially or totally block stimulation, decrease, prevent, delayactivation, inactivate, desensitize, or down regulate signaltransduction. Kinase activators are compounds that, e.g., bind to,stimulate, increase, open, activate, facilitate, enhance activation,sensitize or up regulate signal transduction.

The term “composition” as used herein is intended to encompass a productcomprising the specified ingredients in the specified amounts, as wellas any product which results, directly or indirectly, from combinationof the specified ingredients in the specified amounts. By“pharmaceutically acceptable” it is meant the carrier, diluent orexcipient must be compatible with the other ingredients of theformulation and not deleterious to the recipient thereof.

The “subject” is defined herein to include animals such as mammals,including, but not limited to, primates (e.g., humans), cows, sheep,goats, horses, dogs, cats, rabbits, rats, mice and the like. Inpreferred embodiments, the subject is a human.

Isotope Enriched or Labeled Compounds

Compounds of the invention can exist in isotope-labeled oriostope-enriched form containing one or more atoms having an atomic massor mass number different from the atomic mass or mass number mostabundantly found in nature. Isotopes can be radioactive ornon-radioactive isotopes. Isotopes of atoms such as hydrogen, carbon,phosphorous, sulfur, fluorine, chlorine, and iodine include, but are notlimited to, ²H, ³H, ¹³C, ¹⁴C, ¹⁵N, ¹⁸O, ³²P, ³⁵S, ¹⁸F, ³⁶Cl, and ¹²⁵I.Compounds that contain other isotopes of these and/or other atoms arewithin the scope of this invention.

In another embodiment, the isotope-labeled compounds contain deuterium(²H), tritium (³H) or ¹⁴C isotopes. Isotope-labeled compounds of thisinvention can be prepared by the general methods well known to personshaving ordinary skill in the art. Such isotope-labeled compounds can beconveniently prepared by carrying out the procedures disclosed in theExamples disclosed herein and Schemes by substituting a readilyavailable isotope-labeled reagent for a non-labeled reagent. In someinstances, compounds may be treated with isotope-labeled reagents toexchange a normal atom with its isotope, for example, hydrogen fordeuterium can be exchanged by the action of a deuteric acid such asD₂SO₄/D₂O. In addition to the above, relevant procedures andintermediates are disclosed, for instance, in Lizondo, J et al., DrugsFut, 21(11), 1116 (1996); Brickner, S J et al., J Med Chem, 39(3), 673(1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); PCTpublications WO1997010223, WO2005099353, WO1995007271, WO2006008754;U.S. Pat. Nos. 7,538,189; 7,534,814; 7,531,685; 7,528,131; 7,521,421;7,514,068; 7,511,013; and US Patent Application Publication Nos.20090137457; 20090131485; 20090131363; 20090118238; 20090111840;20090105338; 20090105307; 20090105147; 20090093422; 20090088416; and20090082471, the methods are hereby incorporated by reference.

The isotope-labeled compounds of the invention may be used as standardsto determine the effectiveness in binding assays. Isotope containingcompounds have been used in pharmaceutical research to investigate thein vivo metabolic fate of the compounds by evaluation of the mechanismof action and metabolic pathway of the nonisotope-labeled parentcompound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Suchmetabolic studies are important in the design of safe, effectivetherapeutic drugs, either because the in vivo active compoundadministered to the patient or because the metabolites produced from theparent compound prove to be toxic or carcinogenic (Foster et al.,Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London,1985; Kato et al., J. Labelled Comp. Radiopharmaceut., 36(10):927-932(1995); Kushner et al., Can. J. Physiol. Pharmacol., 77, 79-88 (1999).

In addition, non-radio active isotope containing drugs, such asdeuterated drugs called “heavy drugs,” can be used for the treatment ofdiseases and conditions related to NAMPT activity. Increasing the amountof an isotope present in a compound above its natural abundance iscalled enrichment. Examples of the amount of enrichment include fromabout 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37,42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol%. Replacement of up to about 15% of normal atom with a heavy isotopehas been effected and maintained for a period of days to weeks inmammals, including rodents and dogs, with minimal observed adverseeffects (Czajka D M and Finkel A J, Ann. N.Y. Acad. Sci. 1960 84: 770;Thomson J F, Ann. New York Acad. Sci. 1960 84: 736; Czakja D M et al.,Am. J. Physiol. 1961 201: 357). Acute replacement of as high as 15%-23%in human fluids with deuterium was found not to cause toxicity(Blagojevic N et al. in “Dosimetry & Treatment Planning for NeutronCapture Therapy”, Zamenhof R, Solares G and Harling O Eds. 1994.Advanced Medical Publishing, Madison Wis. pp. 125-134; Diabetes Metab.23: 251 (1997)).

Stable isotope labeling of a drug can alter its physico-chemicalproperties such as pKa and lipid solubility. These effects andalterations can affect the pharmacodynamic response of the drug moleculeif the isotopic substitution affects a region involved in aligand-receptor interaction. While some of the physical properties of astable isotope-labeled molecule are different from those of theunlabeled one, the chemical and biological properties are the same, withone important exception: because of the increased mass of the heavyisotope, any bond involving the heavy isotope and another atom will bestronger than the same bond between the light isotope and that atom.Accordingly, the incorporation of an isotope at a site of metabolism orenzymatic transformation will slow said reactions potentially alteringthe pharmacokinetic profile or efficacy relative to the non-isotopiccompound.

Compounds

Suitable groups for X¹, X², Y¹, R¹, and R² in compounds of Formula (I)are independently selected. The described embodiments of the presentinvention may be combined. Such combination is contemplated and withinthe scope of the present invention. For example, it is contemplated thatembodiments for any of X¹, X², Y¹, R¹, and R² can be combined withembodiments defined for any other of X¹, X², Y¹, R¹, and R².

Embodiments of Formula (I)

One embodiment of this invention, therefore, pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (I)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl,hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl,C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl; wherein each R²C₄-C₆-alkyl, C₄-C₆-alkenyl,and C₄-C₆-alkynyl is substituted with one or more substituentsindependently selected from the group consisting of R³, OR³, SR³,S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂,NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³,NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂,C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³,C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br andI; wherein each R² aryl, 3-12 membered heterocyclyl, cycloalkyl, andcycloalkenyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, SR⁴,S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂,NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴,NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂,C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴,C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R³, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl,and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵,C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵,NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂,NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵,C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂,SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl,cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substitutedwith one or more substituents independently selected from the groupconsisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶,OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶,NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶,NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶,C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸,N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸,NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸,OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹,N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹,NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹,OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, Se,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹,C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹,NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹,NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂,C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹,C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Brand I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenylis optionally substituted with one or more substituents independentlyselected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹²,C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and

R¹², at each occurrence, is independently selected alkyl.

In one embodiment of Formula (I), X¹ is N and X² is CR¹. In anotherembodiment of Formula (I), X¹ is CR¹ and X² is N. In another embodimentof Formula (I), X¹ is CR¹ and X² is CR¹. In another embodiment ofFormula (I), X¹ is CR¹ and X² is CR¹, and R¹, at each occurrence, isindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F,Cl, Br and I. In another embodiment of Formula (I), X¹ is CR¹ and X² isCR¹, and R¹, at each occurrence, is independently selected from thegroup consisting of hydrogen, alkyl, F, Cl, Br and I. In anotherembodiment of Formula (I), X¹ is CR¹ and X² is CR¹, and R¹, at eachoccurrence, is hydrogen.

In one embodiment of Formula (I), R¹, at each occurrence, isindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F,Cl, Br and I. In another embodiment of Formula (I), R¹, at eachoccurrence, is independently selected from the group consisting ofhydrogen, alkyl, F, Cl, Br and I. In another embodiment of Formula (I),R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl. In another embodiment ofFormula (I), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (I), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl.In another embodiment of Formula (I), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl.In another embodiment of Formula (I), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl.

In one embodiment of Formula (I), R² is independently selected from thegroup consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl,3-12 membered heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR²C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with oneor more substituents independently selected from the group consisting ofR³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂,NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³,NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³,NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³,C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R² aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴,N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴,NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴,NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴,C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I. In another embodiment of Formula (I), R² is independentlyselected from the group consisting of C₄-C₆-alkyl, and aryl; whereineach R²C₄-C₆-alkyl is substituted with one or more substituentsindependently selected from the group consisting of R³, F, Cl, Br and I;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, CN, F, Cl, Br and I. In another embodiment ofFormula (I), R² is independently selected from the group consisting ofC₄-C₆-alkyl, and aryl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³; wherein each R² aryl is optionally substituted with oneor more substituents independently selected from the group consisting ofR⁴, OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN. In another embodiment of Formula(I), R² is C₄-C₆-alkyl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³. In another embodiment of Formula (I), R² is aryl;wherein each R² aryl is substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, CO(O)R⁴,C(O)NHR⁴, and CN. In another embodiment of Formula (I), R² is aryl;wherein each R² aryl is substituted with one C(O)NHR⁴. In anotherembodiment of Formula (I), R² is phenyl; wherein each R² phenyl issubstituted with one C(O)NHR⁴. In another embodiment of Formula (I), R²is phenyl; wherein each R² phenyl is substituted with one OR⁴. Inanother embodiment of Formula (I), R² is phenyl; wherein each R² phenylis substituted with one R⁴.

In one embodiment of Formula (I), R³, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein eachR³ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂,NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵,NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵,NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵,C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, andheterocyclyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁶, OR⁶, SR⁶,S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂,NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶,NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂,C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶,C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. Inanother embodiment of Formula (I), R³, at each occurrence, isindependently heterocyclyl; wherein each R³ heterocyclyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of CO(O)R⁶, F, Cl, Br and I. In another embodimentof Formula (I), R³, at each occurrence, is independently heterocyclyl;wherein each R³ heterocyclyl is optionally substituted with one or moreCO(O)R⁶.

In one embodiment of Formula (I), R⁶, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹,C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹,SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃,CF₂CF₃, F, Cl, Br and I. In another embodiment of Formula (I), R⁶, ateach occurrence, is alkyl.

In one embodiment of Formula (I), R⁴, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂,NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷,NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷,NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷,C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein the cyclic moiety represented by R⁴ isindependently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment ofFormula (I), R⁴, at each occurrence, is independently selected from thegroup consisting of alkyl and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, F, Cl, Br and I; wherein thecyclic moiety represented by R⁴ is independently optionally substitutedwith one or more substituents independently selected from the groupconsisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I. Inanother embodiment of Formula (I), R⁴, at each occurrence, isheterocyclyl. In another embodiment of Formula (I), R⁴, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁴is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (I), R⁷, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In anotherembodiment of Formula (I), R⁷, at each occurrence, is independentlyheterocyclyl.

In one embodiment of Formula (I), R¹⁰, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹,OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹,NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹,NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹,C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂,SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂,CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹²,CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹², SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and R¹², at each occurrence, is independentlyselected alkyl. In another embodiment of Formula (I), R¹⁰, at eachoccurrence, is independently selected from the group consisting ofalkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, N(R¹¹)₂,NHC(O)R¹¹, OH, F, Cl, Br and I; wherein each R¹⁰ heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², F, Cl,Br and I; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl. In anotherembodiment of Formula (I), R¹⁰, at each occurrence, is independentlyselected from the group consisting of alkyl, aryl, heterocyclyl, andcycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰heterocyclyl, and cycloalkyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R¹²,and C(O)R¹²; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl.

One embodiment of this invention pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (I)

wherein

X¹ is CR¹ and X² is CR¹;

Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl;

R² is independently selected from the group consisting of C₄-C₆-alkyl,and aryl; wherein each R²C₄-C₆-alkyl is substituted with one or more R³;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN;

R³, at each occurrence, is heterocyclyl; wherein each R³ heterocyclyl isoptionally substituted with one or more CO(O)R⁶;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more R⁷;

R⁶, at each occurrence, is independently alkyl;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ are independentlyoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, andCO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein eachR¹⁰ alkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹¹, OR¹¹, SR¹¹,N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², and C(O)R¹²;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, heterocyclyl, and cycloalkyl; wherein each R¹¹alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl is optionally substituted with alkyl; and

R¹², at each occurrence, is independently selected alkyl.

Still another embodiment pertains to compounds having Formula (I), whichincludes Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118,119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160,161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174,175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188,189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202,203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216,217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230,231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244,245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258,259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272,273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286,287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300,301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314,315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328,329, 330, 331, 332, 333, 334, 335, and pharmaceutically acceptable saltsthereof.

Embodiments of Formula (II)

In another aspect, the present invention provides compounds of Formula(II)

and pharmaceutically acceptable salts thereof; wherein X¹, X², R¹ and R²are as described herein for Formula (I).

One embodiment of this invention pertains to compounds of Formula (II)or pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl,hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl,C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl; wherein each R²C₄-C₆-alkyl, C₄-C₆-alkenyl,and C₄-C₆-alkynyl is substituted with one or more substituentsindependently selected from the group consisting of R³, OR³, SR³,S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂,NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³,NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂,C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³,C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br andI; wherein each R² aryl, 3-12 membered heterocyclyl, cycloalkyl, andcycloalkenyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, SR⁴,S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂,NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴,NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂,C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴,C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R³, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl,and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵,C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵,NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂,NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵,C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂,SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl,cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substitutedwith one or more substituents independently selected from the groupconsisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶,OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶,NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶,NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶,C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, OC(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸,N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸,NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸,OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹,N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹,NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹,OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹,C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹,NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹,NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂,C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹,C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Brand I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenylis optionally substituted with one or more substituents independentlyselected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹²,C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and

R¹², at each occurrence, is independently selected alkyl.

In one embodiment of Formula (II), X¹ is N and X² is CR¹. In anotherembodiment of Formula (II), X¹ is CR¹ and X² is N. In another embodimentof Formula (II), X¹ is CR¹ and X² is CR¹. In another embodiment ofFormula (II), X¹ is CR¹ and X² is CR¹, and R¹, at each occurrence, isindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F,Cl, Br and I. In another embodiment of Formula (II), X¹ is CR¹ and X² isCR¹, and R¹, at each occurrence, is independently selected from thegroup consisting of hydrogen, alkyl, F, Cl, Br and I. In anotherembodiment of Formula (II), X¹ is CR¹ and X² is CR¹, and R¹, at eachoccurrence, is hydrogen.

In one embodiment of Formula (II), R¹, at each occurrence, isindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F,Cl, Br and I. In another embodiment of Formula (II), R¹, at eachoccurrence, is independently selected from the group consisting ofhydrogen, alkyl, F, Cl, Br and I. In another embodiment of Formula (II),R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl. In another embodiment ofFormula (II), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (II), R² is independently selected from thegroup consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl,3-12 membered heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR²C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with oneor more substituents independently selected from the group consisting ofR³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂,NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³,NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³,NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³,C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R² aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴,N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴,NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴,NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴,C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I. In another embodiment of Formula (II), R² is independentlyselected from the group consisting of C₄-C₆-alkyl, and aryl; whereineach R²C₄-C₆-alkyl is substituted with one or more substituentsindependently selected from the group consisting of R³, F, Cl, Br and I;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, CN, F, Cl, Br and I. In another embodiment ofFormula (II), R² is independently selected from the group consisting ofC₄-C₆-alkyl, and aryl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³; wherein each R² aryl is optionally substituted with oneor more substituents independently selected from the group consisting ofR⁴, OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN. In another embodiment of Formula(II), R² is C₄-C₆-alkyl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³. In another embodiment of Formula (II), R² is aryl;wherein each R² aryl is substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, CO(O)R⁴,C(O)NHR⁴, and CN. In another embodiment of Formula (II), R² is aryl;wherein each R² aryl is substituted with one C(O)NHR⁴. In anotherembodiment of Formula (II), R² is phenyl; wherein each R² phenyl issubstituted with one C(O)NHR⁴. In another embodiment of Formula (II), R²is phenyl; wherein each R² phenyl is substituted with one OR⁴. Inanother embodiment of Formula (II), R² is phenyl; wherein each R² phenylis substituted with one R⁴.

In one embodiment of Formula (II), R³, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein eachR³ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂,NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵,NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵,NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵,C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, andheterocyclyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁶, OR⁶, SR⁶,S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂,NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶,NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂,C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶,C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. Inanother embodiment of Formula (II), R³, at each occurrence, isindependently heterocyclyl; wherein each R³ heterocyclyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of CO(O)R⁶, F, Cl, Br and I. In another embodimentof Formula (II), R³, at each occurrence, is independently heterocyclyl;wherein each R³ heterocyclyl is optionally substituted with one or moreCO(O)R⁶.

In one embodiment of Formula (II), R⁶, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹,C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹,SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃,CF₂CF₃, F, Cl, Br and I. In another embodiment of Formula (II), R⁶, ateach occurrence, is alkyl.

In one embodiment of Formula (II), R⁴, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂,NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷,NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷,NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷,C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein the cyclic moiety represented by R⁴ isindependently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment ofFormula (II), R⁴, at each occurrence, is independently selected from thegroup consisting of alkyl and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, F, Cl, Br and I; wherein thecyclic moiety represented by R⁴ is independently optionally substitutedwith one or more substituents independently selected from the groupconsisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I. Inanother embodiment of Formula (II), R⁴, at each occurrence, isheterocyclyl. In another embodiment of Formula (II), R⁴, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁴is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (II), R⁷, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In anotherembodiment of Formula (II), R⁷, at each occurrence, is independentlyheterocyclyl.

In one embodiment of Formula (II), R¹⁰, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹,OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹,NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹,NHC(O)N(R¹¹)₂ NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹,C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂,SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂,CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹²,CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and R¹², at each occurrence, is independentlyselected alkyl. In another embodiment of Formula (II), R¹⁰, at eachoccurrence, is independently selected from the group consisting ofalkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, N(R¹¹)₂,NHC(O)R¹¹, OH, F, Cl, Br and I; wherein each R¹⁰ heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², F, Cl,Br and I; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl. In anotherembodiment of Formula (II), R¹⁰, at each occurrence, is independentlyselected from the group consisting of alkyl, aryl, heterocyclyl, andcycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰heterocyclyl, and cycloalkyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R¹²,and C(O)R¹²; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl.

One embodiment of this invention pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (II)

wherein

X¹ is CR¹ and X² is CR¹;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl;

R² is independently selected from the group consisting of C₄-C₆-alkyl,and aryl; wherein each R²C₄-C₆-alkyl is substituted with one or more R³;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN;

R³, at each occurrence, is heterocyclyl; wherein each R³ heterocyclyl isoptionally substituted with one or more CO(O)R⁶;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more R⁷;

R⁶, at each occurrence, is independently alkyl;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ are independentlyoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, andCO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein eachR¹⁰ alkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹¹, OR¹¹, SR¹¹,N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², and C(O)R¹²;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, heterocyclyl, and cycloalkyl; wherein each R¹¹alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl is optionally substituted with alkyl; and

R¹², at each occurrence, is independently selected alkyl.

Still another embodiment pertains to compounds having Formula (II),which includes Examples 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117,118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131,132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159,160, 161, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174,175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188,189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202,203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216,217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230,231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244,245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258,259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272,273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286,287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300,301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314,315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328,329, 330, 331, 332, 333, 334, 335, and pharmaceutically acceptable saltsthereof.

Embodiments of Formula (III)

In another aspect, the present invention provides compounds of Formula(III)

and pharmaceutically acceptable salts thereof; wherein R^(4x) is asdescribed herein for substituents on R² when R² is aryl in Formula (I).

One embodiment of this invention pertains to compounds of Formula (III)or pharmaceutically acceptable salts thereof;

wherein

R^(4x) is independently selected from the group consisting of R⁴, OR⁴,SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴,N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴,NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴,NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴,C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independentlyoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰,C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰,N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰,NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰,NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰,C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H,C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂,F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹,C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹,NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹,NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂,C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹,C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Brand I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenylis optionally substituted with one or more substituents independentlyselected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹²,C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and

R¹², at each occurrence, is independently selected alkyl.

In one embodiment of Formula (III), R^(4x) is independently selectedfrom the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴,CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴,NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴,NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂,C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴,SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃,OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula(III), R^(4x) is independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, CN, F, Cl, Br and I. In another embodiment ofFormula (III), R^(4x) is independently selected from the groupconsisting of R⁴, OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN. In another embodimentof Formula (III), R^(4x) is C(O)NHR⁴. In another embodiment of Formula(III), R^(4x) is OR⁴. In another embodiment of Formula (III), R^(4x) isR⁴.

In one embodiment of Formula (III), R⁴, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂,NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷,NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷,NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷,C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein the cyclic moiety represented by R⁴ isindependently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment ofFormula (III), R⁴, at each occurrence, is independently selected fromthe group consisting of alkyl and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, F, Cl, Br and I; wherein thecyclic moiety represented by R⁴ is independently optionally substitutedwith one or more substituents independently selected from the groupconsisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I. Inanother embodiment of Formula (III), R⁴, at each occurrence, isheterocyclyl. In another embodiment of Formula (III), R⁴, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁴is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (III), R⁷, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In anotherembodiment of Formula (III), R⁷, at each occurrence, is independentlyheterocyclyl.

In one embodiment of Formula (III), R¹⁰, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹,OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹,NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹,NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹,C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂,SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂,CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹²,CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and R¹², at each occurrence, is independentlyselected alkyl. In another embodiment of Formula (III), R¹⁰, at eachoccurrence, is independently selected from the group consisting ofalkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, N(R¹¹)₂,NHC(O)R¹¹, OH, F, Cl, Br and I; wherein each R¹⁰ heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², F, Cl,Br and I; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl. In anotherembodiment of Formula (III), R¹⁰, at each occurrence, is independentlyselected from the group consisting of alkyl, aryl, heterocyclyl, andcycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰heterocyclyl, and cycloalkyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R¹²,and C(O)R¹²; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl.

One embodiment of this invention pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (III)

wherein

R^(4x) is independently selected from the group consisting of R⁴, OR⁴,CO(O)R⁴, C(O)NHR⁴, and CN;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more R⁷;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moiety represented by R⁴ is independently optionallysubstituted with one or more substituents independently selected fromthe group consisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, and CO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein eachR¹⁰ alkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹¹, OR¹¹, SR¹¹,N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², and C(O)R¹²;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, heterocyclyl, and cycloalkyl; wherein each R¹¹alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl is optionally substituted with alkyl; and

R¹², at each occurrence, is independently selected alkyl.

Still another embodiment pertains to compounds having Formula (III),which includes Examples 1, 2, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 114, 115, 117, 118, 119, 120, 121, 122,123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136,137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150,151, 152, 153, 154, 155, 157, 158, 159, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, andpharmaceutically acceptable salts thereof.

Embodiments of Formula (IA)

One embodiment of this invention, therefore, pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (IA)

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl,hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl,C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl; wherein each R²C₄-C₆-alkyl, C₄-C₆-alkenyl,and C₄-C₆-alkynyl is substituted with one or more substituentsindependently selected from the group consisting of R³, OR³, SR³,S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂,NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³,NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂,C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³,C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br andI; wherein each R² aryl, 3-12 membered heterocyclyl, cycloalkyl, andcycloalkenyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, SR⁴,S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂,NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴,NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂,C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴,C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R³, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl,and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵,C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵,NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂,NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵,C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂,SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl,cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substitutedwith one or more substituents independently selected from the groupconsisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶,OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶,NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶,NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶,C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸,N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸,NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸,OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹,N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹,NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹,OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, Se,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁶SO₂R¹⁶, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹,C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹,NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹,NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂,C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹,C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Brand I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenylis optionally substituted with one or more substituents independentlyselected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹²,C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and

R¹², at each occurrence, is independently selected alkyl.

In one embodiment of Formula (IA), X¹ is N and X² is CR¹. In anotherembodiment of Formula (IA), X¹ is CR¹ and X² is N. In another embodimentof Formula (IA), X¹ is CR¹ and X² is CR¹. In another embodiment ofFormula (IA), X¹ is CR¹ and X² is CR¹, and R¹, at each occurrence, isindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F,Cl, Br and I. In another embodiment of Formula (IA), X¹ is CR¹ and X² isCR¹, and R¹, at each occurrence, is independently selected from thegroup consisting of hydrogen, alkyl, F, Cl, Br and I. In anotherembodiment of Formula (IA), X¹ is CR¹ and X² is CR¹, and R¹, at eachoccurrence, is hydrogen.

In one embodiment of Formula (IA), R¹, at each occurrence, isindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F,Cl, Br and I. In another embodiment of Formula (IA), R¹, at eachoccurrence, is independently selected from the group consisting ofhydrogen, alkyl, F, Cl, Br and I. In another embodiment of Formula (IA),R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl. In another embodiment ofFormula (IA), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IA), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl.In another embodiment of Formula (IA), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl.In another embodiment of Formula (IA), Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl.

In one embodiment of Formula (IA), R² is independently selected from thegroup consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl,3-12 membered heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR²C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with oneor more substituents independently selected from the group consisting ofR³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂,NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³,NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³,NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³,C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R² aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴,N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴,NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴,NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴,C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I. In another embodiment of Formula (IA), R² is independentlyselected from the group consisting of C₄-C₆-alkyl, and aryl; whereineach R²C₄-C₆-alkyl is substituted with one or more substituentsindependently selected from the group consisting of R³, F, Cl, Br and I;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, CN, F, Cl, Br and I. In another embodiment ofFormula (IA), R² is independently selected from the group consisting ofC₄-C₆-alkyl, and aryl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³; wherein each R² aryl is optionally substituted with oneor more substituents independently selected from the group consisting ofR⁴, OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN. In another embodiment of Formula(IA), R² is C₄-C₆-alkyl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³. In another embodiment of Formula (IA), R² is aryl;wherein each R² aryl is substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, CO(O)R⁴,C(O)NHR⁴, and CN. In another embodiment of Formula (IA), R² is aryl;wherein each R² aryl is substituted with one C(O)NHR⁴. In anotherembodiment of Formula (IA), R² is phenyl; wherein each R² phenyl issubstituted with one C(O)NHR⁴. In another embodiment of Formula (IA), R²is phenyl; wherein each R² phenyl is substituted with one OR⁴. Inanother embodiment of Formula (IA), R² is phenyl; wherein each R² phenylis substituted with one R⁴.

In one embodiment of Formula (IA), R³, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein eachR³ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂,NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵,NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵,NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵,C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, andheterocyclyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁶, OR⁶, SR⁶,S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂,NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶,NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂,C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶,C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. Inanother embodiment of Formula (IA), R³, at each occurrence, isindependently heterocyclyl; wherein each R³ heterocyclyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of CO(O)R⁶, F, Cl, Br and I. In another embodimentof Formula (IA), R³, at each occurrence, is independently heterocyclyl;wherein each R³ heterocyclyl is optionally substituted with one or moreCO(O)R⁶.

In one embodiment of Formula (IA), R⁶, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹,C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹,SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃,CF₂CF₃, F, Cl, Br and I. In another embodiment of Formula (IA), R⁶, ateach occurrence, is alkyl.

In one embodiment of Formula (IA), R⁴, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂,NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷,NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷,NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷,C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein the cyclic moiety represented by R⁴ isindependently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment ofFormula (IA), R⁴, at each occurrence, is independently selected from thegroup consisting of alkyl and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, F, Cl, Br and I; wherein thecyclic moiety represented by R⁴ is independently optionally substitutedwith one or more substituents independently selected from the groupconsisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I. Inanother embodiment of Formula (IA), R⁴, at each occurrence, isheterocyclyl. In another embodiment of Formula (IA), R⁴, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁴is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (IA), R⁷, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In anotherembodiment of Formula (IA), R⁷, at each occurrence, is independentlyheterocyclyl. In another embodiment of Formula (IA), R⁷, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁷is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (IA), R¹⁰, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹,OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)_(R) ¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹,NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹,NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹,C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂,SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂,CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹²,CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹²)₂, C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and R¹², at each occurrence, is independentlyselected alkyl. In another embodiment of Formula (IA), R¹⁰, at eachoccurrence, is independently selected from the group consisting ofalkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, N(R¹¹)₂,NHC(O)R¹¹, OH, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², F, Cl,Br and I; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl. In anotherembodiment of Formula (IA), R¹⁰, at each occurrence, is independentlyselected from the group consisting of alkyl, aryl, heterocyclyl, andcycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ aryl,heterocyclyl, and cycloalkyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R¹²,C(O)R¹², and F; R¹¹, at each occurrence, is independently selected fromthe group consisting of alkyl, heterocyclyl, and cycloalkyl; whereineach R¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl.

One embodiment of this invention pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (IA)

wherein

X¹ is CR¹ and X² is CR¹;

Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl;

R² is independently selected from the group consisting of C₄-C₆-alkyl,and aryl; wherein each R²C₄-C₆-alkyl is substituted with one or more R³;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN;

R³, at each occurrence, is heterocyclyl; wherein each R³ heterocyclyl isoptionally substituted with one or more CO(O)R⁶;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more R⁷;

R⁶, at each occurrence, is independently alkyl;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independentlyoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, andCO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein eachR¹⁰ alkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹¹, OR¹¹, SR¹¹,N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ aryl, heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², and F;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, heterocyclyl, and cycloalkyl; wherein each R¹¹alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl is optionally substituted with alkyl; and

R¹², at each occurrence, is independently selected alkyl.

Still another embodiment pertains to compounds having Formula (IA),which include

-   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(5-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(6-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   methyl 4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)benzoate;-   N-(4-cyanophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)butyl]piperidine-1-carboxylate;-   N-{4-[1-(2,2-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(methylsulfanyl)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(methylsulfanyl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[3-(pyrrolidin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]pyrrolidine-1-carboxylate;-   tert-butyl    (3R)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    (3S)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]azetidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]azetidine-1-carboxylate;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy]phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(2-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   tert-butyl    4-[4-({[3-(4-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   N-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(2-fluoropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   N-{4-[(1-pentanoylazetidin-3-yl)oxy}phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-propanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(morpholin-4-ylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(4-methylpiperazin-1-yl)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(N,N-dimethyl-beta-alanyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(pyrrolidin-1-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(2-fluoropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(4-chloropyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(2-chloropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   4-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)piperazine-1-carboxamide;-   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-cyclopropylethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(5-oxo-L-prolyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-oxopropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-pentanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(bicyclo[2.2.1]hept-2-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-D-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-L-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(4-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N-acetyl-L-leucyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-propanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(ethoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4[(1-acetylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;    and pharmaceutically acceptable salts thereof.    Embodiments of Formula (IIA)

In another aspect, the present invention provides compounds of Formula(IIA)

and pharmaceutically acceptable salts thereof; wherein X¹, X², R¹ and R²are as described herein for Formula (IA).

One embodiment of this invention pertains to compounds of Formula (IIA)or pharmaceutically acceptable salts thereof;

wherein

X¹ is N and X² is CR¹; or

X¹ is CR¹ and X² is N; or

X¹ is CR¹ and X² is CR¹;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl,hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I;

R² is independently selected from the group consisting of C₄-C₆-alkyl,C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl; wherein each R²C₄-C₆-alkyl, C₄-C₆-alkenyl,and C₄-C₆-alkynyl is substituted with one or more substituentsindependently selected from the group consisting of R³, OR³, SR³,S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂, NHR³, N(R³)₂,NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³, NR³C(O)OR³,NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³, NR³C(O)N(R³)₂,C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³, C(O)NHSO₂R³,C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br andI; wherein each R² aryl, 3-12 membered heterocyclyl, cycloalkyl, andcycloalkenyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, SR⁴,S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂,NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴,NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂,C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴,C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R³, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl,and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵,C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵,NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂,NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵,C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂,SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl,cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substitutedwith one or more substituents independently selected from the groupconsisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶,OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶,NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶,NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶,C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁵, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁵ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸,N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸, C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸,NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸, SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸,OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl, Br and I;

R⁶, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹,N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹,NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹,OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁸, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

R⁹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

wherein the cyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹are independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, Se,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁶SO₂R¹⁶, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹,C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹,NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹,NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂,C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹,C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Brand I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenylis optionally substituted with one or more substituents independentlyselected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹²,C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and

R¹², at each occurrence, is independently selected alkyl.

In one embodiment of Formula (IIA), X¹ is N and X² is CR¹. In anotherembodiment of Formula (IIA), X¹ is CR¹ and X² is N. In anotherembodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹. In anotherembodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹, and R¹, at eachoccurrence, is independently selected from the group consisting ofhydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH,NH₂, CN, NO₂, F, Cl, Br and I. In another embodiment of Formula (IIA),X¹ is CR¹ and X² is CR¹, and R¹, at each occurrence, is independentlyselected from the group consisting of hydrogen, alkyl, F, Cl, Br and I.In another embodiment of Formula (IIA), X¹ is CR¹ and X² is CR¹, and R¹,at each occurrence, is hydrogen.

In one embodiment of Formula (IIA), R¹, at each occurrence, isindependently selected from the group consisting of hydrogen, alkyl,alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxy, OH, NH₂, CN, NO₂, F,Cl, Br and I. In another embodiment of Formula (IIA), R¹, at eachoccurrence, is independently selected from the group consisting ofhydrogen, alkyl, F, Cl, Br and I. In another embodiment of Formula(IIA), R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl. In another embodiment ofFormula (IIA), R¹, at each occurrence, is hydrogen.

In one embodiment of Formula (IIA), R² is independently selected fromthe group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl, aryl,3-12 membered heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR²C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substituted with oneor more substituents independently selected from the group consisting ofR³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³, OC(O)OR³, NH₂,NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³, NHC(O)OR³,NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³,NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³,C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R² aryl, 3-12 membered heterocyclyl,cycloalkyl, and cycloalkenyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴,N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴,NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴,NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴,C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I. In another embodiment of Formula (IIA), R² is independentlyselected from the group consisting of C₄-C₆-alkyl, and aryl; whereineach R²C₄-C₆-alkyl is substituted with one or more substituentsindependently selected from the group consisting of R³, F, Cl, Br and I;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, CN, F, Cl, Br and I. In another embodiment ofFormula (IIA), R² is independently selected from the group consisting ofC₄-C₆-alkyl, and aryl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³; wherein each R² aryl is optionally substituted with oneor more substituents independently selected from the group consisting ofR⁴, OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN. In another embodiment of Formula(IIA), R² is C₄-C₆-alkyl; wherein each R²C₄-C₆-alkyl is substituted withone or more R³. In another embodiment of Formula (IIA), R² is aryl;wherein each R² aryl is substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, CO(O)R⁴,C(O)NHR⁴, and CN. In another embodiment of Formula (IIA), R² is aryl;wherein each R² aryl is substituted with one C(O)NHR⁴. In anotherembodiment of Formula (IIA), R² is phenyl; wherein each R² phenyl issubstituted with one C(O)NHR⁴. In another embodiment of Formula (IIA),R² is phenyl; wherein each R² phenyl is substituted with one OR⁴. Inanother embodiment of Formula (IIA), R² is phenyl; wherein each R²phenyl is substituted with one R⁴.

In one embodiment of Formula (IIA), R³, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, cycloalkyl, cycloalkenyl, and heterocyclyl; wherein eachR³ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵, C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂,NHR⁵, N(R⁵)₂, NHC(O)R⁵, NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵,NR⁵C(O)OR⁵, NHC(O)NH₂, NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵,NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵,C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂, SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein each R³ aryl, cycloalkyl, cycloalkenyl, andheterocyclyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁶, OR⁶, SR⁶,S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶, OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂,NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶, NHC(O)OR⁶, NR⁶C(O)OR⁶,NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶, NR⁶C(O)N(R⁶)₂,C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶, C(O)NHSO₂R⁶,C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. Inanother embodiment of Formula (IIA), R³, at each occurrence, isindependently heterocyclyl; wherein each R³ heterocyclyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of CO(O)R⁶, F, Cl, Br and I. In another embodimentof Formula (IIA), R³, at each occurrence, is independently heterocyclyl;wherein each R³ heterocyclyl is optionally substituted with one or moreCO(O)R⁶.

In one embodiment of Formula (IIA), R⁶, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁶ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁹, OR⁹, SR⁹, S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹,C(O)N(R⁹)₂, NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹,SO₂N(R⁹)₂, NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃,CF₂CF₃, F, Cl, Br and I. In another embodiment of Formula (IIA), R⁶, ateach occurrence, is alkyl.

In one embodiment of Formula (IIA), R⁴, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂,NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷,NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷,NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷,C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein the cyclic moiety represented by R⁴ isindependently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, Se,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁶C(O)NHR¹⁶, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment ofFormula (IIA), R⁴, at each occurrence, is independently selected fromthe group consisting of alkyl and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, F, Cl, Br and I; wherein thecyclic moiety represented by R⁴ is independently optionally substitutedwith one or more substituents independently selected from the groupconsisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I. Inanother embodiment of Formula (IIA), R⁴, at each occurrence, isheterocyclyl. In another embodiment of Formula (IIA), R⁴, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁴is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (IIA), R⁷, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In anotherembodiment of Formula (IIA), R⁷, at each occurrence, is independentlyheterocyclyl. In another embodiment of Formula (IIA), R⁷, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁷is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (IIA), R¹⁰, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹,OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹,NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹,NHC(O)N(R¹¹)₂ NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹,C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂,SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂,CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R¹⁰aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹²,CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and R¹², at each occurrence, is independentlyselected alkyl. In another embodiment of Formula (IIA), R¹⁰, at eachoccurrence, is independently selected from the group consisting ofalkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, N(R¹¹)₂,NHC(O)R¹¹, OH, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², F, Cl,Br and I; R¹¹, at each occurrence, is independently selected from thegroup consisting of alkyl, heterocyclyl, and cycloalkyl; wherein eachR¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl. In anotherembodiment of Formula (IIA), R¹⁰, at each occurrence, is independentlyselected from the group consisting of alkyl, aryl, heterocyclyl, andcycloalkyl; wherein each R¹⁰ alkyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ aryl,heterocyclyl, and cycloalkyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R¹²,C(O)R¹², and F; R¹¹, at each occurrence, is independently selected fromthe group consisting of alkyl, heterocyclyl, and cycloalkyl; whereineach R¹¹ alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl.

One embodiment of this invention pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (IIA)

wherein

X¹ is CR¹ and X² is CR¹;

R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, F, and Cl;

R² is independently selected from the group consisting of C₄-C₆-alkyl,and aryl; wherein each R²C₄-C₆-alkyl is substituted with one or more R³;wherein each R² aryl is optionally substituted with one or moresubstituents independently selected from the group consisting of R⁴,OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN;

R³, at each occurrence, is heterocyclyl; wherein each R³ heterocyclyl isoptionally substituted with one or more CO(O)R⁶;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more R⁷;

R⁶, at each occurrence, is independently alkyl;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independentlyoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹⁰, C(O)C(O)R¹⁰, and CO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein eachR¹⁰ alkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹¹, OR¹¹, SR¹¹,N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ aryl, heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², and F;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, heterocyclyl, and cycloalkyl; wherein each R¹¹alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl is optionally substituted with alkyl; and

R¹², at each occurrence, is independently selected alkyl.

Still another embodiment pertains to compounds having Formula (IIA),which include

-   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(5-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(6-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1[(2R)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   methyl 4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)benzoate;-   N-(4-cyanophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)butyl]piperidine-1-carboxylate;-   N-{4-[1-(2,2-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(methylsulfanyl)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(methylsulfanyl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[3-(pyrrolidin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]pyrrolidine-1-carboxylate;-   tert-butyl    (3R)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    (3S)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]azetidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]azetidine-1-carboxylate;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(2-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   tert-butyl    4-[4-({[3-(4-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   N-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   tert-butyl    4-[4-({[3-(2-fluoropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;-   N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-propanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(morpholin-4-ylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(4-methylpiperazin-1-yl)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(N,N-dimethyl-beta-alanyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(pyrrolidin-1-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(2-fluoropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(4-chloropyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(2-chloropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-cyclopropylethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(5-oxo-L-prolyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-oxopropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-pentanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(bicyclo[2.2.1]hept-2-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-D-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-L-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(4-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N-acetyl-L-leucyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-propanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(ethoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   3-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-acetylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;    and pharmaceutically acceptable salts thereof.    Embodiments of Formula (IIIA)

In another aspect, the present invention provides compounds of Formula(IIIA)

and pharmaceutically acceptable salts thereof; wherein R^(4x) is asdescribed herein for substituents on R² when R² is aryl in Formula (IA).

One embodiment of this invention pertains to compounds of Formula (IIIA)or pharmaceutically acceptable salts thereof;

wherein

R^(4x) is independently selected from the group consisting of R⁴, OR⁴,SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴,N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴,NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴,NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴,C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I;

R⁷, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl;

wherein the cyclic moieties represented by R⁴ and R⁷ are independentlyoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰, S(O)R¹⁰,C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰, NH₂, NHR¹⁰,N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰, NHC(O)OR¹⁰,NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂, NR¹⁰C(O)NHR¹⁰,NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂, C(O)NHOH, C(O)NHOR¹⁰,C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰, SO₂N(R¹⁰)₂, C(O)H,C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂,F, Cl, Br and I;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹⁰ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹,C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹, OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹,NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹,NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂,C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹,C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Brand I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl, and cycloalkenylis optionally substituted with one or more substituents independentlyselected from the group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹²,C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and

R¹², at each occurrence, is independently selected alkyl.

In one embodiment of Formula (IIIA), R^(4x) is independently selectedfrom the group consisting of R⁴, OR⁴, SR⁴, S(O)R⁴, SO₂R⁴, C(O)R⁴,CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂, NHC(O)R⁴, NR⁴C(O)R⁴,NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴, NHC(O)NH₂, NHC(O)NHR⁴,NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂, C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂,C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴, C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴,SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃,OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment of Formula(IIIA), R^(4x) is independently selected from the group consisting ofR⁴, OR⁴, CO(O)R⁴, C(O)NHR⁴, CN, F, Cl, Br and I. In another embodimentof Formula (IIIA), R^(4x) is independently selected from the groupconsisting of R⁴, OR⁴, CO(O)R⁴, C(O)NHR⁴, and CN. In another embodimentof Formula (IIIA), R^(4x) is C(O)NHR⁴. In another embodiment of Formula(IIIA), R^(4x) is OR⁴. In another embodiment of Formula (IIIA), R^(4x)is R⁴.

In one embodiment of Formula (IIIA), R⁴, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁴ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷, C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂,NHR⁷, N(R⁷)₂, NHC(O)R⁷, NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷,NR⁷C(O)OR⁷, NHC(O)NH₂, NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷,NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷, C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷,C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂, SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F,Cl, Br and I; wherein the cyclic moiety represented by R⁴ isindependently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR^(10c) (O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂)C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I. In another embodiment ofFormula (IIIA), R⁴, at each occurrence, is independently selected fromthe group consisting of alkyl and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, F, Cl, Br and I; wherein thecyclic moiety represented by R⁴ is independently optionally substitutedwith one or more substituents independently selected from the groupconsisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I. Inanother embodiment of Formula (IIIA), R⁴, at each occurrence, isheterocyclyl. In another embodiment of Formula (IIIA), R⁴, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁴is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (IIIA), R⁷, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl. In anotherembodiment of Formula (IIIA), R⁷, at each occurrence, is independentlyheterocyclyl. In another embodiment of Formula (IIIA), R⁷, at eachoccurrence, is heterocyclyl; wherein the cyclic moiety represented by R⁷is independently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, C(O)C(O)R¹⁰,C(O)R¹⁰, CO(O)R¹⁰, F, Cl, Br and I.

In one embodiment of Formula (IIIA), R¹⁰, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)¹¹, OC(O)R¹¹, OC(O)OR¹¹,NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹, NHC(O)OR¹¹,NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹, NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹,NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹, C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹,C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂, SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H,C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂, CNOH, CNOCH₃, OH, (O), CN, N₃,NO₂, F, Cl, Br and I; wherein each R¹⁰ aryl, heterocyclyl, cycloalkyl,and cycloalkenyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², OR¹², SR¹²,S(O)R¹², SO₂R¹², C(O)R¹², CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹²,N(R¹²)₂, NHC(O)R¹², NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹²,NR¹²C(O)OR¹², NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹²,NR¹²C(O)N(R¹²)₂, C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹²,C(O)NHSO₂R¹², C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H,C(O)OH, C(N)NH₂, C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂,F, Cl, Br and I; R¹¹, at each occurrence, is independently selected fromthe group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl,cycloalkyl, and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, andalkynyl is optionally substituted with alkyl or alkoxy; wherein each R¹¹aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionallysubstituted with alkyl or alkoxy; and R¹², at each occurrence, isindependently selected alkyl. In another embodiment of Formula (IIIA),R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein eachR¹⁰ alkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹¹, OR¹¹, SR¹¹,N(R¹¹)₂)NHC(O)R¹¹, OH, F, Cl, Br and I; wherein each R¹⁰ aryl,heterocyclyl, and cycloalkyl is optionally substituted with one or moresubstituents independently selected from the group consisting of R¹²,C(O)R¹², F, Cl, Br and I; R¹¹, at each occurrence, is independentlyselected from the group consisting of alkyl, heterocyclyl, andcycloalkyl; wherein each R¹¹ alkyl is optionally substituted withalkoxy; wherein each R¹¹ heterocyclyl and cycloalkyl is optionallysubstituted with alkyl; and R¹², at each occurrence, is independentlyselected alkyl. In another embodiment of Formula (IIIA), R¹⁰, at eachoccurrence, is independently selected from the group consisting ofalkyl, aryl, heterocyclyl, and cycloalkyl; wherein each R¹⁰ alkyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹¹, OR¹¹, SR¹¹, N(R¹¹)₂,NHC(O)R¹¹, OH, and F; wherein each R¹⁰ aryl, heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², and F;R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, heterocyclyl, and cycloalkyl; wherein each R¹¹alkyl is optionally substituted with alkoxy; wherein each R¹¹heterocyclyl and cycloalkyl is optionally substituted with alkyl; andR¹², at each occurrence, is independently selected alkyl.

One embodiment of this invention pertains to compounds orpharmaceutically acceptable salts thereof, which are useful asinhibitors of NAMPT, the compounds having Formula (IIIA)

wherein

R^(4x) is independently selected from the group consisting of R⁴, OR⁴,CO(O)R⁴, C(O)NHR⁴, and CN;

R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, and heterocyclyl; wherein each R⁴ alkyl isoptionally substituted with one or more R⁷;

R⁷, at each occurrence, is independently heterocyclyl;

wherein the cyclic moiety represented by R⁴ and R⁷ are independentlyoptionally substituted with one or more substituents independentlyselected from the group consisting of R¹⁰, C(O)C(O)R¹⁰, C(O)R¹⁰, andCO(O)R¹⁰;

R¹⁰, at each occurrence, is independently selected from the groupconsisting of alkyl, aryl, heterocyclyl, and cycloalkyl; wherein eachR¹⁰ alkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹¹, OR¹¹, SR¹¹,N(R¹¹)₂, NHC(O)R¹¹, OH, and F; wherein each R¹⁰ aryl, heterocyclyl, andcycloalkyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R¹², C(O)R¹², and F;

R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, heterocyclyl, and cycloalkyl; wherein each R¹¹alkyl is optionally substituted with alkoxy;

wherein each R¹¹ heterocyclyl is optionally substituted with alkyl; and

R¹², at each occurrence, is independently selected alkyl.

Still another embodiment pertains to compounds having Formula (IIIA),which include

-   N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;    03-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   methyl 4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)benzoate;-   N-(4-cyanophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(methylsulfanyl)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(methylsulfanyl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({1-[3-(pyrrolidin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylpiperidin-4-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]pyrrolidine-1-carboxylate;-   tert-butyl    (3R)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    (3S)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]azetidine-1-carboxylate;-   tert-butyl    3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]azetidine-1-carboxylate;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3S)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(ethoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(methoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-butanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-propanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2,2-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3-methylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(2-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopropylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(morpholin-4-ylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(4-methylpiperazin-1-yl)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(N,N-dimethyl-beta-alanyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(cyclopentylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[1-(pyrrolidin-1-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(N-acetyl-L-leucyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-butylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-cyclopropylethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopropylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylpentyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2-methylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-ethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-pentanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-{4-[1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(5-oxo-L-prolyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-ethoxypropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(4-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-acetylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-(1-propanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;-   N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(ethoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2-oxopropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(methoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-{4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-pentanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[1-(bicyclo[2.2.1]hept-2-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-D-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(5-oxo-L-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(4-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(N-acetyl-L-leucyl)pyrrolidin-3-yl]oxy}-phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-propanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;-   N-[4-({(3R)-1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-[4-({(3R)-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(ethoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;-   N-(4-{[(3R)-1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;    and pharmaceutically acceptable salts thereof.    Pharmaceutical Compositions, Combination Therapies, Methods of    Treatment, and Administration

Another embodiment comprises pharmaceutical compositions comprising acompound having Formula (I) and an excipient.

Still another embodiment comprises methods of treating cancer in amammal comprising administering thereto a therapeutically acceptableamount of a compound having Formula (I).

Still another embodiment pertains to compositions for treating diseasesduring which NAMPT is expressed, said compositions comprising anexcipient and a therapeutically effective amount of the compound havingFormula (I).

Still another embodiment pertains to methods of treating disease in apatient during which NAMPT is expressed, said methods comprisingadministering to the patient a therapeutically effective amount of acompound having Formula (I).

Still another embodiment pertains to compositions for treatinginflammatory and tissue repair disorders; particularly rheumatoidarthritis, inflammatory bowel disease, asthma and COPD (chronicobstructive pulmonary disease), osteoarthritis, osteoporosis andfibrotic diseases; dermatosis, including psoriasis, atopic dermatitisand ultra-violet induced skin damage; autoimmune diseases includingsystemic lupus erythematosis, multiple sclerosis, psoriatic arthritis,ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease,stroke, athersclerosis, restenosis, diabetes, glomerulonephritis,cancer, particularly wherein the cancer is selected from breast,prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas,leukemia, lymphoma or Hodgkin's disease, cachexia, inflammationassociated with infection and certain viral infections, includingAcquired Immune Deficiency Syndrome (AIDS), adult respiratory distresssyndrome, and ataxia telengiectasia, said compositions comprising anexcipient and a therapeutically effective amount of the compound havingFormula (I).

Still another embodiment pertains to methods of treating inflammatoryand tissue repair disorders; particularly rheumatoid arthritis,inflammatory bowel disease, asthma and COPD (chronic obstructivepulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases;dermatosis, including psoriasis, atopic dermatitis and ultra-violetinduced skin damage; autoimmune diseases including systemic lupuserythematosis, multiple sclerosis, psoriatic arthritis, ankylosingspondylitis, tissue and organ rejection, Alzheimer's disease, stroke,athersclerosis, restenosis, diabetes, glomerulonephritis, cancer,particularly wherein the cancer is selected from breast, prostate, lung,colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphomaor Hodgkin's disease, cachexia, inflammation associated with infectionand certain viral infections, including Acquired Immune DeficiencySyndrome (AIDS), adult respiratory distress syndrome, and ataxiatelengiectasia in a patient, said methods comprising administering tothe patient a therapeutically effective amount of a compound havingFormula (I).

Still another embodiment pertains to compositions for treating diseasesduring which NAMPT is expressed, said compositions comprising anexcipient and a therapeutically effective amount of the compound havingFormula (I) and a therapeutically effective amount of one additionaltherapeutic agent or more than one additional therapeutic agent.

Still another embodiment pertains to methods of treating disease in apatient during which NAMPT is expressed, said methods comprisingadministering to the patient a therapeutically effective amount of acompound having Formula (I) and a therapeutically effective amount ofone additional therapeutic agent or more than one additional therapeuticagent.

Still another embodiment pertains to compositions for treatinginflammatory and tissue repair disorders; particularly rheumatoidarthritis, inflammatory bowel disease, asthma and COPD (chronicobstructive pulmonary disease), osteoarthritis, osteoporosis andfibrotic diseases; dermatosis, including psoriasis, atopic dermatitisand ultra-violet induced skin damage; autoimmune diseases includingsystemic lupus erythematosis, multiple sclerosis, psoriatic arthritis,ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease,stroke, athersclerosis, restenosis, diabetes, glomerulonephritis,cancer, particularly wherein the cancer is selected from breast,prostate, lung, colon, cervix, ovary, skin, CNS, bladder, pancreas,leukemia, lymphoma or Hodgkin's disease, cachexia, inflammationassociated with infection and certain viral infections, includingAcquired Immune Deficiency Syndrome (AIDS), adult respiratory distresssyndrome, and ataxia telengiectasia, said compositions comprising anexcipient and a therapeutically effective amount of the compound havingFormula (I) and a therapeutically effective amount of one additionaltherapeutic agent or more than one additional therapeutic agent.

Still another embodiment pertains to methods of treating inflammatoryand tissue repair disorders; particularly rheumatoid arthritis,inflammatory bowel disease, asthma and COPD (chronic obstructivepulmonary disease), osteoarthritis, osteoporosis and fibrotic diseases;dermatosis, including psoriasis, atopic dermatitis and ultra-violetinduced skin damage; autoimmune diseases including systemic lupuserythematosis, multiple sclerosis, psoriatic arthritis, ankylosingspondylitis, tissue and organ rejection, Alzheimer's disease, stroke,athersclerosis, restenosis, diabetes, glomerulonephritis, cancer,particularly wherein the cancer is selected from breast, prostate, lung,colon, cervix, ovary, skin, CNS, bladder, pancreas, leukemia, lymphomaor Hodgkin's disease, cachexia, inflammation associated with infectionand certain viral infections, including Acquired Immune DeficiencySyndrome (AIDS), adult respiratory distress syndrome, and ataxiatelengiectasia in a patient, said methods comprising administering tothe patient a therapeutically effective amount of the compound havingFormula (I) and a therapeutically effective amount of one additionaltherapeutic agent or more than one additional therapeutic agent.

Metabolites of compounds having Formula (I), produced by in vitro or invivo metabolic processes, may also have utility for treating diseasesassociated with NAMPT.

Certain precursor compounds which may be metabolized in vitro or in vivoto form compounds having Formula (I) may also have utility for treatingdiseases associated with NAMPT.

Compounds having Formula (I) may exist as acid addition salts, basicaddition salts or zwitterions. Salts of the compounds are preparedduring isolation or following purification of the compounds. Acidaddition salts of the compounds are those derived from the reaction ofthe compounds with an acid. For example, the acetate, adipate, alginate,bicarbonate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate,butyrate, camphorate, camphorsulfonate, digluconate, formate, fumarate,glycerophosphate, glutamate, hemisulfate, heptanoate, hexanoate,hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate,maleate, mesitylenesulfonate, methanesulfonate, naphthylenesulfonate,nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate,propionate, succinate, tartrate, thiocyanate, trichloroacetic,trifluoroacetic, para-toluenesulfonate, and undecanoate salts of thecompounds are contemplated as being embraced by this invention. Basicaddition salts of the compounds are those derived from the reaction ofthe compounds with the hydroxide, carbonate or bicarbonate of cationssuch as lithium, sodium, potassium, calcium, and magnesium.

The compounds having Formula (I) may be administered, for example,bucally, ophthalmically, orally, osmotically, parenterally(intramuscularly, intraperitoneally intrasternally, intravenously,subcutaneously), rectally, topically, transdermally or vaginally.

Therapeutically effective amounts of compounds having Formula (I) dependon the recipient of the treatment, the disorder being treated and theseverity thereof, the composition containing the compound, the time ofadministration, the route of administration, the duration of treatment,the compound potency, its rate of clearance and whether or not anotherdrug is co-administered. The amount of a compound of this inventionhaving Formula (I) used to make a composition to be administered dailyto a patient in a single dose or in divided doses is from about 0.03 toabout 200 mg/kg body weight. Single dose compositions contain theseamounts or a combination of submultiples thereof.

Compounds having Formula (I) may be administered with or without anexcipient. Excipients include, for example, encapsulating materials oradditives such as absorption accelerators, antioxidants, binders,buffers, coating agents, coloring agents, diluents, disintegratingagents, emulsifiers, extenders, fillers, flavoring agents, humectants,lubricants, perfumes, preservatives, propellants, releasing agents,sterilizing agents, sweeteners, solubilizers, wetting agents andmixtures thereof.

Excipients for preparation of compositions comprising a compound havingFormula (I) to be administered orally in solid dosage form include, forexample, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzylbenzoate, 1,3-butylene glycol, carbomers, castor oil, cellulose,cellulose acetate, cocoa butter, corn starch, corn oil, cottonseed oil,cross-povidone, diglycerides, ethanol, ethyl cellulose, ethyl laureate,ethyl oleate, fatty acid esters, gelatin, germ oil, glucose, glycerol,groundnut oil, hydroxypropylmethyl cellulose, isopropanol, isotonicsaline, lactose, magnesium hydroxide, magnesium stearate, malt,mannitol, monoglycerides, olive oil, peanut oil, potassium phosphatesalts, potato starch, povidone, propylene glycol, Ringer's solution,safflower oil, sesame oil, sodium carboxymethyl cellulose, sodiumphosphate salts, sodium lauryl sulfate, sodium sorbitol, soybean oil,stearic acids, stearyl fumarate, sucrose, surfactants, talc, tragacanth,tetrahydrofurfuryl alcohol, triglycerides, water, and mixtures thereof.Excipients for preparation of compositions comprising a compound of thisinvention having Formula (I) to be administered ophthalmically or orallyin liquid dosage forms include, for example, 1,3-butylene glycol, castoroil, corn oil, cottonseed oil, ethanol, fatty acid esters of sorbitan,germ oil, groundnut oil, glycerol, isopropanol, olive oil, polyethyleneglycols, propylene glycol, sesame oil, water and mixtures thereof.Excipients for preparation of compositions comprising a compound of thisinvention having Formula (I) to be administered osmotically include, forexample, chlorofluorohydrocarbons, ethanol, water and mixtures thereof.Excipients for preparation of compositions comprising a compound of thisinvention having Formula (I) to be administered parenterally include,for example, 1,3-butanediol, castor oil, corn oil, cottonseed oil,dextrose, germ oil, groundnut oil, liposomes, oleic acid, olive oil,peanut oil, Ringer's solution, safflower oil, sesame oil, soybean oil,U.S.P. or isotonic sodium chloride solution, water and mixtures thereof.Excipients for preparation of compositions comprising a compound of thisinvention having Formula (I) to be administered rectally or vaginallyinclude, for example, cocoa butter, polyethylene glycol, wax andmixtures thereof.

Compounds having Formula (I) are expected to be useful when used withalkylating agents, angiogenesis inhibitors, antibodies, antimetabolites,antimitotics, antiproliferatives, antivirals, aurora kinase inhibitors,apoptosis promoters (for example, Bcl-xL, Bcl-w and Bfl-1) inhibitors,activators of death receptor pathway, Bcr-Abl kinase inhibitors, BiTE(Bi-Specific T cell Engager) antibodies, antibody drug conjugates,biologic response modifiers, cyclin-dependent kinase inhibitors, cellcycle inhibitors, cyclooxygenase-2 inhibitors, DVDs, leukemia viraloncogene homolog (ErbB2) receptor inhibitors, growth factor inhibitors,heat shock protein (HSP)-90 inhibitors, histone deacetylase (HDAC)inhibitors, hormonal therapies, immunologicals, inhibitors of inhibitorsof apoptosis proteins (IAPs), intercalating antibiotics, kinaseinhibitors, kinesin inhibitors, Jak2 inhibitors, mammalian target ofrapamycin inhibitors, microRNA's, mitogen-activated extracellularsignal-regulated kinase inhibitors, multivalent binding proteins,non-steroidal anti-inflammatory drugs (NSAIDs), poly ADP (adenosinediphosphate)-ribose polymerase (PARP) inhibitors, platinumchemotherapeutics, polo-like kinase (Plk) inhibitors, phosphoinositide-3kinase (PI3K) inhibitors, proteosome inhibitors, purine analogs,pyrimidine analogs, receptor tyrosine kinase inhibitors,retinoids/deltoids plant alkaloids, small inhibitory ribonucleic acids(siRNAs), topoisomerase inhibitors, ubiquitin ligase inhibitors, and thelike, and in combination with one or more of these agents.

BiTE antibodies are bi-specific antibodies that direct T-cells to attackcancer cells by simultaneously binding the two cells. The T-cell thenattacks the target cancer cell. Examples of BiTE antibodies includeadecatumumab (Micromet MT201), blinatumomab (Micromet MT103) and thelike. Without being limited by theory, one of the mechanisms by whichT-cells elicit apoptosis of the target cancer cell is by exocytosis ofcytolytic granule components, which include perforin and granzyme B.

SiRNAs are molecules having endogenous RNA bases or chemically modifiednucleotides. The modifications do not abolish cellular activity, butrather impart increased stability and/or increased cellular potency.Examples of chemical modifications include phosphorothioate groups,2′-deoxynucleotide, 2′-OCH₃-containing ribonucleotides,2′-F-ribonucleotides, 2′-methoxyethyl ribonucleotides, combinationsthereof and the like. The siRNA can have varying lengths (e.g., 10-200bps) and structures (e.g., hairpins, single/double strands, bulges,nicks/gaps, mismatches) and are processed in cells to provide activegene silencing. A double-stranded siRNA (dsRNA) can have the same numberof nucleotides on each strand (blunt ends) or asymmetric ends(overhangs). The overhang of 1-2 nucleotides can be present on the senseand/or the antisense strand, as well as present on the 5′- and/or the3′-ends of a given strand.

Multivalent binding proteins are binding proteins comprising two or moreantigen binding sites. Multivalent binding proteins are engineered tohave the three or more antigen binding sites and are generally notnaturally occurring antibodies. The term “multispecific binding protein”means a binding protein capable of binding two or more related orunrelated targets. Dual variable domain (DVD) binding proteins aretetravalent or multivalent binding proteins binding proteins comprisingtwo or more antigen binding sites. Such DVDs may be monospecific (i.e.,capable of binding one antigen) or multispecific (i.e., capable ofbinding two or more antigens). DVD binding proteins comprising two heavychain DVD polypeptides and two light chain DVD polypeptides are referredto as DVD Ig's. Each half of a DVD Ig comprises a heavy chain DVDpolypeptide, a light chain DVD polypeptide, and two antigen bindingsites. Each binding site comprises a heavy chain variable domain and alight chain variable domain with a total of 6 CDRs involved in antigenbinding per antigen binding site.

Alkylating agents include altretamine, AMD-473, AP-5280, apaziquone,bendamustine, brostallicin, busulfan, carboquone, carmustine (BCNU),chlorambucil, CLORETAZINE® (laromustine, VNP 40101M), cyclophosphamide,decarbazine, estramustine, fotemustine, glufosfamide, ifosfamide,KW-2170, lomustine (CCNU), mafosfamide, melphalan, mitobronitol,mitolactol, nimustine, nitrogen mustard N-oxide, ranimustine,temozolomide, thiotepa, TREANDA® (bendamustine), treosulfan,trofosfamide and the like.

Angiogenesis inhibitors include endothelial-specific receptor tyrosinekinase (Tie-2) inhibitors, epidermal growth factor receptor (EGFR)inhibitors, insulin growth factor-2 receptor (IGFR-2) inhibitors, matrixmetalloproteinase-2 (MMP-2) inhibitors, matrix metalloproteinase-9(MMP-9) inhibitors, platelet-derived growth factor receptor (PDGFR)inhibitors, thrombospondin analogs, vascular endothelial growth factorreceptor tyrosine kinase (VEGFR) inhibitors and the like.

Antimetabolites include ALIMTA® (pemetrexed disodium, LY231514, MTA),5-azacitidine, XELODA® (capecitabine), carmofur, LEUSTAT® (cladribine),clofarabine, cytarabine, cytarabine ocfosfate, cytosine arabinoside,decitabine, deferoxamine, doxifluridine, eflornithine, EICAR(5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide), enocitabine,ethnylcytidine, fludarabine, 5-fluorouracil alone or in combination withleucovorin, GEMZAR® (gemcitabine), hydroxyurea, ALKERAN® (melphalan),mercaptopurine, 6-mercaptopurine riboside, methotrexate, mycophenolicacid, nelarabine, nolatrexed, ocfosfate, pelitrexol, pentostatin,raltitrexed, Ribavirin, triapine, trimetrexate, S-1, tiazofurin,tegafur, TS-1, vidarabine, UFT and the like.

Antivirals include ritonavir, hydroxychloroquine and the like.

Aurora kinase inhibitors include ABT-348, AZD-1152, MLN-8054, VX-680,Aurora A-specific kinase inhibitors, Aurora B-specific kinase inhibitorsand pan-Aurora kinase inhibitors and the like.

Bcl-2 protein inhibitors include AT-101 ((−)gossypol), GENASENSE® (G3139or oblimersen (Bcl-2-targeting antisense oligonucleotide)), IPI-194,IPI-565,N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide)(ABT-737),N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide(ABT-263), GX-070 (obatoclax) and the like.

Bcr-Abl kinase inhibitors include DASATINIB® (BMS-354825), GLEEVEC®(imatinib) and the like.

CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584,flavopyridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib(CYC-202, R-roscovitine), ZK-304709 and the like.

COX-2 inhibitors include ABT-963, ARCOXIA® (etoricoxib), BEXTRA®(valdecoxib), BMS347070, CELEBREX® (celecoxib), COX-189 (lumiracoxib),CT-3, DERAMAXX® (deracoxib), JTE-522,4-methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl-1H-pyrrole), MK-663(etoricoxib), NS-398, parecoxib, RS-57067, SC-58125, SD-8381, SVT-2016,S-2474, T-614, VIOXX® (rofecoxib) and the like.

EGFR inhibitors include ABX-EGF, anti-EGFR immunoliposomes, EGF-vaccine,EMD-7200, ERBITUX® (cetuximab), HR3, IgA antibodies, IRESSA®(gefitinib), TARCEVA® (erlotinib or OSI-774), TP-38, EGFR fusionprotein, TYKERB® (lapatinib) and the like.

ErbB2 receptor inhibitors include CP-724-714, CI-1033 (canertinib),HERCEPTIN® (trastuzumab), TYKERB® (lapatinib), OMNITARG® (2C4,petuzumab), TAK-165, GW-572016 (ionafarnib), GW-282974, EKB-569, PI-166,dHER2 (HER2 vaccine), APC-8024 (HER-2 vaccine), anti-HER/2neu bispecificantibody, B7.her2IgG3, AS HER2 trifunctional bispecfic antibodies, mABAR-209, mAB 2B-1 and the like.

Histone deacetylase inhibitors include depsipeptide, LAQ-824, MS-275,trapoxin, suberoylanilide hydroxamic acid (SAHA), TSA, valproic acid andthe like.

HSP-90 inhibitors include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010,CNF-2024, 17-DMAG, geldanamycin, IPI-504, KOS-953, MYCOGRAB® (humanrecombinant antibody to HSP-90), NCS-683664, PU24FCl, PU-3, radicicol,SNX-2112, STA-9090 VER49009 and the like.

Inhibitors of inhibitors of apoptosis proteins include HGS1029,GDC-0145, GDC-0152, LCL-161, LBW-242 and the like.

Antibody drug conjugates include anti-CD22-MC-MMAF, anti-CD22-MC-MMAE,anti-CD22-MCC-DM1, CR-011-vcMMAE, PSMA-ADC, MEDI-547, SGN-19Am SGN-35,SGN-75 and the like

Activators of death receptor pathway include TRAIL, antibodies or otheragents that target TRAIL or death receptors (e.g., DR4 and DR5) such asApomab, conatumumab, ETR2-ST01, GDC0145 (lexatumumab), HGS-1029,LBY-135, PRO-1762 and trastuzumab.

Kinesin inhibitors include Eg5 inhibitors such as AZD4877, ARRY-520;CENPE inhibitors such as GSK923295A and the like.

JAK-2 inhibitors include CEP-701 (lesaurtinib), XL019 and INCB018424 andthe like.

MEK inhibitors include ARRY-142886, ARRY-438162 PD-325901, PD-98059 andthe like.

mTOR inhibitors include AP-23573, CCI-779, everolimus, RAD-001,rapamycin, temsirolimus, ATP-competitive TORC1/TORC2 inhibitors,including PI-103, PP242, PP30, Torin 1 and the like.

Non-steroidal anti-inflammatory drugs include AMIGESIC® (salsalate),DOLOBID® (diflunisal), MOTRIN® (ibuprofen), ORUDIS® (ketoprofen),RELAFEN® (nabumetone), FELDENE® (piroxicam), ibuprofen cream, ALEVE®(naproxen) and NAPROSYN® (naproxen), VOLTAREN® (diclofenac), INDOCIN®(indomethacin), CLINORIL® (sulindac), TOLECTIN® (tolmetin), LODINE®(etodolac), TORADOL® (ketorolac), DAYPRO® (oxaprozin) and the like.

PDGFR inhibitors include C-451, CP-673, CP-868596 and the like.

Platinum chemotherapeutics include cisplatin, ELOXATIN® (oxaliplatin)eptaplatin, lobaplatin, nedaplatin, PARAPLATIN® (carboplatin),satraplatin, picoplatin and the like.

Polo-like kinase inhibitors include BI-2536 and the like.

Phosphoinositide-3 kinase (PI3K) inhibitors include wortmannin,LY294002, XL-147, CAL-120, ONC-21, AEZS-127, ETP-45658, PX-866,GDC-0941, BGT226, BEZ235, XL765 and the like.

Thrombospondin analogs include ABT-510, ABT-567, ABT-898, TSP-1 and thelike.

VEGFR inhibitors include AVASTIN® (bevacizumab), ABT-869, AEE-788,ANGIOZYME™ (a ribozyme that inhibits angiogenesis (RibozymePharmaceuticals (Boulder, Colo.) and Chiron, (Emeryville, Calif.)),axitinib (AG-13736), AZD-2171, CP-547,632, IM-862, MACUGEN (pegaptamib),NEXAVAR® (sorafenib, BAY43-9006), pazopanib (GW-786034), vatalanib(PTK-787, ZK-222584), SUTENT® (sunitinib, SU-11248), VEGF trap, ZACTIMA™(vandetanib, ZD-6474) and the like.

Antibiotics include intercalating antibiotics aclarubicin, actinomycinD, amrubicin, annamycin, adriamycin, BLENOXANE® (bleomycin),daunorubicin, CAELYX® or MYOCET® (liposomal doxorubicin), elsamitrucin,epirbucin, glarbuicin, ZAVEDOS® (idarubicin), mitomycin C, nemorubicin,neocarzinostatin, peplomycin, pirarubicin, rebeccamycin, stimalamer,streptozocin, VALSTAR® (valrubicin), zinostatin and the like.

Topoisomerase inhibitors include aclarubicin, 9-aminocamptothecin,amonafide, amsacrine, becatecarin, belotecan, BN-80915, CAMPTOSAR®(irinotecan hydrochloride), camptothecin, CARDIOXANE® (dexrazoxine),diflomotecan, edotecarin, ELLENCE® or PHARMORUBICIN® (epirubicin),etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan,mitoxantrone, orathecin, pirarbucin, pixantrone, rubitecan, sobuzoxane,SN-38, tafluposide, topotecan and the like.

Antibodies include AVASTIN® (bevacizumab), CD40-specific antibodies,chTNT-1/B, denosumab, ERBITUX® (cetuximab), HUMAX-CD4® (zanolimumab),IGF1R-specific antibodies, lintuzumab, PANOREX® (edrecolomab), RENCAREX®(WX G250), RITUXAN® (rituximab), ticilimumab, trastuzimab, CD20antibodies types I and II and the like.

Hormonal therapies include ARIMIDEX® (anastrozole), AROMASIN(exemestane), arzoxifene, CASODEX® (bicalutamide), CETROTIDE®(cetrorelix), degarelix, deslorelin, DESOPAN® (trilostane),dexamethasone, DROGENIL® (flutamide), EVISTA® (raloxifene), AFEMA™(fadrozole), FARESTON® (toremifene), FASLODEX® (fulvestrant), FEMARA®(letrozole), formestane, glucocorticoids, HECTOROL® (doxercalciferol),RENAGEL® (sevelamer carbonate), lasofoxifene, leuprolide acetate,MEGACE® (megesterol), MIFEPREX® (mifepristone), NILANDRON™ (nilutamide),NOLVADEX® (tamoxifen citrate), PLENAXIS™ (abarelix), prednisone,PROPECIA® (finasteride), rilostane, SUPREFACT® (buserelin), TRELSTAR®(luteinizing hormone releasing hormone (LHRH)), VANTAS® (Histrelinimplant), VETORYL® (trilostane or modrastane), ZOLADEX® (fosrelin,goserelin) and the like.

Deltoids and retinoids include seocalcitol (EB1089, CB1093),lexacalcitrol (KH1060), fenretinide, PANRETIN® (aliretinoin), ATRAGEN®(liposomal tretinoin), TARGRETIN® (bexarotene), LGD-1550 and the like.

PARP inhibitors include ABT-888 (veliparib), olaparib, KU-59436,AZD-2281, AG-014699, BSI-201, BGP-15, INO-1001, ONO-2231 and the like.

Plant alkaloids include, but are not limited to, vincristine,vinblastine, vindesine, vinorelbine and the like.

Proteasome inhibitors include VELCADE® (bortezomib), MG132, NPI-0052,PR-171 and the like.

Examples of immunologicals include interferons and otherimmune-enhancing agents. Interferons include interferon alpha,interferon alpha-2a, interferon alpha-2b, interferon beta, interferongamma-1a, ACTIMMUNE® (interferon gamma-1b) or interferon gamma-n1,combinations thereof and the like. Other agents include ALFAFERONE®,(IFN-α), BAM-002 (oxidized glutathione), BEROMUN® (tasonermin), BEXXAR®(tositumomab), CAMPATH® (alemtuzumab), CTLA4 (cytotoxic lymphocyteantigen 4), decarbazine, denileukin, epratuzumab, GRANOCYTE®(lenograstim), lentinan, leukocyte alpha interferon, imiquimod, MDX-010(anti-CTLA-4), melanoma vaccine, mitumomab, molgramostim, MYLOTARG™(gemtuzumab ozogamicin), NEUPOGEN® (filgrastim), OncoVAC-CL, OVAREX®(oregovomab), pemtumomab (Y-muHMFG1), PROVENGE® (sipuleucel-T),sargaramostim, sizofilan, teceleukin, THERACYS® (BacillusCalmette-Guerin), ubenimex, VIRULIZIN® (immunotherapeutic, LorusPharmaceuticals), Z-100 (Specific Substance of Maruyama (SSM)), WF-10(Tetrachlorodecaoxide (TCDO)), PROLEUKIN® (aldesleukin), ZADAXIN®(thymalfasin), ZENAPAX® (daclizumab), ZEVALIN® (90Y-Ibritumomabtiuxetan) and the like.

Biological response modifiers are agents that modify defense mechanismsof living organisms or biological responses, such as survival, growth ordifferentiation of tissue cells to direct them to have anti-tumoractivity and include krestin, lentinan, sizofuran, picibanil PF-3512676(CpG-8954), ubenimex and the like.

Pyrimidine analogs include cytarabine (ara C or Arabinoside C), cytosinearabinoside, doxifluridine, FLUDARA® (fludarabine), 5-FU(5-fluorouracil), floxuridine, GEMZAR® (gemcitabine), TOMUDEX®(ratitrexed), TROXATYL™ (triacetyluridine troxacitabine) and the like.

Purine analogs include LANVIS® (thioguanine) and PURI-NETHOL®(mercaptopurine).

Antimitotic agents include batabulin, epothilone D (KOS-862),N-(2-((4-hydroxyphenyl)amino)pyridin-3-yl)-4-methoxybenzenesulfonamide,ixabepilone (BMS 247550), paclitaxel, TAXOTERE® (docetaxel), PNU100940(109881), patupilone, XRP-9881 (larotaxel), vinflunine, ZK-EPO(synthetic epothilone) and the like.

Ubiquitin ligase inhibitors include MDM2 inhibitors, such as nutlins,NEDD8 inhibitors such as MLN4924 and the like.

Compounds of this invention can also be used as radiosensitizers thatenhance the efficacy of radiotherapy. Examples of radiotherapy includeexternal beam radiotherapy, teletherapy, brachytherapy and sealed,unsealed source radiotherapy and the like.

Additionally, compounds having Formula (I) may be combined with otherchemotherapeutic agents such as ABRAXANE™ (ABI-007), ABT-100 (farnesyltransferase inhibitor), ADVEXIN® (Ad5CMV-p53 vaccine), ALTOCOR® orMEVACOR® (lovastatin), AMPLIGEN® (poly I:poly C12U, a synthetic RNA),APTOSYN® (exisulind), AREDIA® (pamidronic acid), arglabin,L-asparaginase, atamestane (1-methyl-3,17-dione-androsta-1,4-diene),AVAGE® (tazarotene), AVE-8062 (combreastatin derivative) BEC2(mitumomab), cachectin or cachexin (tumor necrosis factor), canvaxin(vaccine), CEAVAC® (cancer vaccine), CELEUK® (celmoleukin), CEPLENE®(histamine dihydrochloride), CERVARIX® (human papillomavirus vaccine),CHOP® (C: CYTOXAN® (cyclophosphamide); H: ADRIAMYCIN®(hydroxydoxorubicin); O: Vincristine (ONCOVIN®); P: prednisone), CYPAT™(cyproterone acetate), combrestatin A4P, DAB(389)EGF (catalytic andtranslocation domains of diphtheria toxin fused via a His-Ala linker tohuman epidermal growth factor) or TransMID-107R™ (diphtheria toxins),dacarbazine, dactinomycin, 5,6-dimethylxanthenone-4-acetic acid (DMXAA),eniluracil, EVIZON™ (squalamine lactate), DIMERICINE® (T4N5 liposomelotion), discodermolide, DX-8951f (exatecan mesylate), enzastaurin,EP0906 (epithilone B), GARDASIL® (quadrivalent human papillomavirus(Types 6, 11, 16, 18) recombinant vaccine), GASTRIMMUNE®, GENASENSE®,GMK (ganglioside conjugate vaccine), GVAX® (prostate cancer vaccine),halofuginone, histerelin, hydroxycarbamide, ibandronic acid, IGN-101,IL-13-PE38, IL-13-PE38QQR (cintredekin besudotox), IL-13-pseudomonasexotoxin, interferon-α, interferon-γ, JUNOVAN™ or MEPACT™ (mifamurtide),lonafarnib, 5,10-methylenetetrahydrofolate, miltefosine(hexadecylphosphocholine), NEOVASTAT® (AE-941), NEUTREXIN® (trimetrexateglucuronate), NIPENT® (pentostatin), ONCONASE® (a ribonuclease enzyme),ONCOPHAGE® (melanoma vaccine treatment), ONCOVAX® (IL-2 Vaccine),ORATHECIN™ (rubitecan), OSIDEM® (antibody-based cell drug), OVAREX® MAb(murine monoclonal antibody), paclitaxel, PANDIMEX™ (aglycone saponinsfrom ginseng comprising 20(S)protopanaxadiol (aPPD) and20(S)protopanaxatriol (aPPT)), panitumumab, PANVAC®-VF (investigationalcancer vaccine), pegaspargase, PEG Interferon A, phenoxodiol,procarbazine, rebimastat, REMOVAB® (catumaxomab), REVLIMID®(lenalidomide), RSR13 (efaproxiral), SOMATULINE® LA (lanreotide),SORIATANE® (acitretin), staurosporine (Streptomyces staurospores),talabostat (PT100), TARGRETIN® (bexarotene), TAXOPREXIN®(DHA-paclitaxel), TELCYTA® (canfosfamide, TLK286), temilifene, TEMODAR®(temozolomide), tesmilifene, thalidomide, THERATOPE® (STn-KLH), thymitaq(2-amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)quinazolinedihydrochloride), TNFERADE™ (adenovector: DNA carrier containing thegene for tumor necrosis factor-α), TRACLEER® or ZAVESCA® (bosentan),tretinoin (Retin-A), tetrandrine, TRISENOX® (arsenic trioxide),VIRULIZIN®, ukrain (derivative of alkaloids from the greater celandineplant), vitaxin (anti-alphavbeta3 antibody), XCYTRIN® (motexafingadolinium), XINLAY™ (atrasentan), XYOTAX™ (paclitaxel poliglumex),YONDELIS® (trabectedin), ZD-6126, ZINECARD® (dexrazoxane), ZOMETA®(zolendronic acid), zorubicin and the like.

Data

Determination of the utility of compounds having Formula (I) as bindersto and inhibitors of NAMPT was performed using Time-ResolvedFluorescence Resonance Energy Transfer (TR-FRET) binding assays.

Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) BindingAssay of NAMPT

Test compounds were serially diluted (typically 11 half log dilutions)in neat DMSO to 50× final concentrations prior to dilution with assaybuffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl₂, 1 mM DTT,1% Glycerol) to 3× and 6% DMSO. Six L were transferred to 384-welllow-volume plates (Owens Corning #3673). To this, 12 L of a 1.5×solution containing enzyme, probe and antibody were added. Finalconcentrations in the 18 L reactions were 1× assay buffer, 2% DMSO, 6.8nM NAMPT (human, recombinant, C-terminally His-tagged), 200 nM probe (apotent nicotinamide-competitive inhibitor conjugated to Oregon Green488) and 1 nM Tb-anti-His antibody (Invitrogen #PV5895). Reactions wereequilibrated at room temperature for 3 hours prior to reading on anEnvision multi-label plate reader (Perkin Elmer; Ex=337 nm, Em=520 and495 nm). Time-resolved FRET ratios (Em₅₂₀/Em₄₉₅) were normalized tocontrols, plotted as a function of compound concentration and fit withthe four-parameter logistic equation to determine IC50s.

Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) BindingAssay of NAMPT with PRPP

Compound handling and data processing were identical to the assay in theabsence of substrates (above). Final concentrations were 1× assaybuffer, 2% DMSO, 2 nM NAMPT, 2 nM probe, 1 nM Tb-anti-His antibody(Invitrogen #PV5895), 200 M PRPP and 2.5 mM ATP. Reactions wereequilibrated for 16 hours prior to measurement to allow for potentialenzymatic modification of test compounds.

Table 1 shows the utility of compounds having Formula I to functionallyinhibit NAMPT.

TABLE 1 TR- FRET TR- Binding - FRET IC50 Binding - (with IC50 PRPP)Example (μM) (μM) 1 0.024900 0.000873 2 0.125000 0.000370 3 1.2200000.007640 4 0.019700 0.000195 5 0.056800 0.000169 6 0.053400 0.000224 70.057800 0.000344 8 0.617000 0.015400 9 0.016300 0.000346 10 0.0415000.000250 11 0.015800 0.000320 12 0.032100 0.000430 13 0.201000 0.00037414 0.879000 0.000178 15 0.307000 0.000917 16 nd nd 17 0.016900 0.00056818 0.036700 0.000294 19 0.153000 0.000860 20 0.068400 0.000500 210.032500 0.000381 22 0.143000 0.000630 23 0.097800 0.000551 24 0.1700000.000988 25 0.037400 0.000362 26 0.073600 0.000724 27 0.013000 0.00024328 0.077200 0.000218 29 0.053400 0.000243 30 0.069400 0.000255 310.040600 0.000330 32 0.018800 0.000209 33 0.056100 0.000430 34 0.0507000.000264 35 0.089200 0.000492 36 0.027300 0.000169 37 0.085400 0.00017438 0.034300 0.000201 39 0.090500 0.000338 40 0.050500 0.000419 410.076800 0.000448 42 0.043800 0.000270 43 0.023700 0.000234 44 0.0446000.000315 45 0.034300 0.000223 46 0.093100 0.000226 47 0.030300 0.00026848 0.206000 0.000169 49 0.150000 0.000245 50 0.015600 0.000169 510.017200 0.000303 52 0.038900 0.000169 53 0.076200 0.000194 54 0.1170000.000169 55 0.029300 0.000169 56 0.027400 0.000169 57 0.006850 0.00022258 0.017400 0.000169 59 0.038500 0.000364 60 0.055400 0.000169 610.020900 0.000310 62 0.091500 0.000467 63 0.044600 0.000390 64 0.0521000.000171 65 0.056600 0.000169 66 0.086000 0.000169 67 0.173000 0.00017168 0.086200 0.000169 69 0.044800 0.000169 70 0.092200 0.000421 710.020100 0.000184 72 0.065600 0.000211 73 0.156000 0.000663 74 0.0311000.000357 75 0.103000 0.000169 76 0.083600 0.000169 77 0.061900 0.00016978 0.137000 0.000226 79 0.092900 0.000169 80 0.122000 0.000169 810.030900 0.000169 82 0.009730 0.000169 83 0.007220 0.000169 84 0.0594000.000169 85 0.117000 0.000325 86 0.027400 0.000244 87 0.019800 0.00016988 0.269000 0.000580 89 0.227000 0.000169 90 0.404000 0.000196 910.320000 0.000169 92 0.387000 0.000169 93 0.138000 0.000169 94 0.4880000.000213 95 0.079100 0.000169 96 0.265000 0.000169 97 0.168000 0.00016998 0.616000 0.001190 99 0.223000 0.000414 100 0.108000 0.000309 1010.143000 0.000629 102 0.095700 0.000286 103 0.296000 0.000287 1040.188000 0.000389 105 0.068300 0.000208 106 0.204000 0.000553 1070.012300 0.000342 108 0.122000 0.000411 109 0.306000 0.000596 1100.035300 0.000421 111 0.053900 0.000292 112 0.043500 0.045900 1130.075800 0.014700 114 0.015800 0.000189 115 0.009220 0.000169 1160.026700 0.000744 117 0.018800 0.000327 118 0.036000 0.000324 1190.117000 0.000978 120 0.145000 0.000689 121 0.018600 0.000497 1220.016600 0.000588 123 0.014700 0.000169 124 0.014900 0.000375 1250.029300 0.000271 126 0.014400 0.000401 127 0.093400 0.000603 1280.030400 0.000519 129 0.040000 0.000401 130 0.084700 0.000559 1310.007720 0.000491 132 0.019100 0.000634 133 0.013200 0.000358 1340.054200 0.000317 135 0.028100 0.000376 136 0.015000 0.000544 1370.098800 0.000440 138 0.011400 0.000596 139 0.014400 0.000442 1400.043000 0.000181 141 0.017600 0.000249 142 0.024600 0.000339 1430.136000 0.000763 144 0.025600 0.000313 145 0.090500 0.000600 1460.015100 0.000270 147 0.016700 0.000169 148 0.027700 0.000321 1490.022100 0.000219 150 0.435000 0.002850 151 0.020800 0.000169 1520.005180 0.000420 153 0.012400 0.000436 154 0.024000 0.000169 1550.399000 0.000425 156 0.002710 0.000237 157 0.022600 0.000169 1580.026300 0.000169 159 0.032400 0.000169 160 0.034700 0.004270 1610.008620 0.005790 162 0.357000 0.000574 163 0.007230 0.000295 1640.015900 0.000313 165 0.014400 0.000389 166 0.017200 0.000337 1670.008410 0.000319 168 0.028900 0.000503 169 0.005360 0.000304 1700.007070 0.000364 171 0.008740 0.000231 172 0.005650 0.000206 1730.090400 0.000393 174 0.020800 0.000325 175 0.030700 0.000403 1760.065500 0.000350 177 0.015800 0.000304 178 0.013900 0.000420 1790.032500 0.000249 180 0.021300 0.000284 181 0.008060 0.000256 1820.003680 0.000219 183 0.022000 0.000380 184 0.018500 0.000305 1850.003230 0.000228 186 0.002930 0.000345 187 0.039300 0.000292 1880.002100 0.000188 189 0.022600 0.000210 190 0.002000 0.000282 1910.004270 0.000291 192 0.023000 0.000255 193 0.014400 0.000243 1940.248000 0.000592 195 0.004190 0.000281 196 0.015000 0.000281 1970.017800 0.000505 198 0.064200 0.000341 199 0.128000 0.000356 2000.036400 0.000382 201 0.043200 0.000313 202 0.051100 0.000327 2030.250000 0.000427 204 0.048600 0.000349 205 0.042600 0.000242 2060.049100 0.000260 207 0.451000 0.000370 208 0.048600 0.000473 2090.024000 0.000694 210 0.206000 0.000356 211 0.055900 0.000341 2120.040900 0.000464 213 0.087300 0.000352 214 0.075800 0.000289 2150.027400 0.000294 216 0.018400 0.000256 217 0.278000 0.000320 2180.171000 0.000451 219 0.019400 0.000290 220 0.010400 0.000340 2210.152000 0.000319 222 0.010700 0.000183 223 0.021600 0.000391 2240.026000 0.000333 225 0.014000 0.000268 226 0.169000 0.000440 2270.069200 0.000294 228 0.019600 0.000310 229 0.040300 0.000314 2300.038800 0.000305 231 0.421000 0.000225 232 0.352000 0.000181 2330.653000 0.000335 234 0.760000 0.000529 235 0.649000 0.000213 2360.667000 0.000210 237 0.581000 0.000257 238 4.010000 0.001410 2391.680000 0.000200 240 0.603000 0.000466 241 0.359000 0.000255 2420.374000 0.000225 243 1.270000 0.000326 244 1.170000 0.000516 2450.317000 0.000169 246 0.437000 0.000213 247 0.871000 0.000304 2480.990000 0.000228 249 0.193000 0.000169 250 0.865000 0.000679 2510.382000 0.000365 252 0.526000 0.000296 253 0.538000 0.000207 2540.246000 0.000174 255 0.271000 0.000173 256 0.830000 0.000169 2570.598000 0.000223 258 0.052400 0.000359 259 0.054500 0.000452 2600.038400 0.000302 261 0.033500 0.000194 262 0.060400 0.000252 2630.143000 0.000239 264 0.040900 0.000188 265 0.191000 0.000169 2660.096200 0.000169 267 0.022500 0.000297 268 0.036500 0.000225 2690.020100 0.000169 270 0.008170 0.000196 271 0.046900 0.000279 2720.090700 0.000241 273 0.203000 0.000169 274 0.082200 0.000264 2750.038300 0.000363 276 0.012400 0.000347 277 0.076700 0.000169 2780.019700 0.000213 279 0.092100 0.000204 280 0.101000 0.000169 2810.065600 0.000169 282 0.026600 0.000219 283 0.033700 0.000266 2840.018300 0.000204 285 0.017200 0.000169 286 0.009760 0.000169 2870.030100 0.000189 288 0.117000 0.000227 289 0.029600 0.000204 2900.011100 0.000224 291 0.025800 0.000207 292 0.268000 0.000259 2930.056600 0.000210 294 0.044300 0.000200 295 0.050700 0.000272 2960.026400 0.000243 297 0.056600 0.000236 298 0.035200 0.000169 2990.064900 0.000451 300 0.052600 0.000341 301 0.059000 0.000243 3020.337000 0.000393 303 0.040500 0.000595 304 0.594000 0.000343 3050.435000 0.000211 306 0.507000 0.000169 307 0.024300 0.000197 3080.024200 0.000293 309 0.032800 0.000262 310 0.004540 0.000297 3110.144000 0.000592 312 0.311000 0.000290 313 0.369000 0.000187 3140.110000 0.000178 315 0.048700 0.000169 316 0.013600 0.000169 3170.029900 0.000207 318 0.125000 0.000419 319 0.070600 0.000426 3200.208000 0.000407 321 0.176000 0.000246 322 0.034900 0.000169 3230.041400 0.000194 324 0.020700 0.000360 325 0.018800 0.000362 3260.032200 0.000294 327 0.450000 0.000169 328 0.159000 0.000344 3290.030400 0.000276 330 0.021900 0.000364 331 0.081000 0.000351 3320.061700 0.000474 333 0.056100 0.000416 334 0.094900 0.000449 3350.045700 0.000495 nd = no data

NAMPT Cell Proliferation Assay

PC3 cells were seeded in 96-well black plates (Corning #3904) at 500cells/well in 90 l of RPMI media containing 10% heat-inactivated FBS andincubated overnight at 37° C. and 5% CO₂ to allow cells to attach towells. The following day, test compounds were serially diluted in neatDMSO to 1000× final concentrations prior to dilution with RPMI media to10× and 1% DMSO. Ten L of the 10× compounds were then transferred towells containing cells to produce a dose response of 10-fold dilutionsfrom 10 M to 1×10⁻⁵ M. Cells were incubated for 5 days at 37° C. and 5%CO₂, then cell viability was measured using Cell Titer Glo reagent(Promega #G7571). Percent inhibition values were calculated and fittedto a sigmoidal dose response curves using Assay Explorer software todetermine IC50s. To assess whether inhibition of cell viability was dueto NAMPT inhibition, the proliferation assay was also performed in thepresence of 0.3 mM nicotinamide mononucleotide.

Table 2 shows the results of the cell proliferation assay.

TABLE 2 Cell Titer- Glo - IC50 Example (μM) 1 0.0117 2 0.0349 3 4.68 40.014 5 0.0283 6 0.0306 7 0.0385 8 7.03 9 0.00682 10 0.0389 11 0.0093312 0.0101 13 0.514 14 6.68 15 0.0999 16 nd 17 0.0368 18 0.0658 19 0.19220 0.123 21 0.0337 22 0.276 23 0.195 24 0.113 25 0.0271 26 0.172 270.0092 28 0.0642 29 0.0661 30 0.125 31 0.0389 32 0.0587 33 0.0687 340.0624 35 0.0902 36 0.0595 37 0.0729 38 0.0836 39 0.115 40 0.0264 410.0698 42 0.10 43 0.028 44 0.0385 45 0.0634 46 0.0442 47 0.064 48 0.095849 0.0801 50 0.00857 51 0.00178 52 0.00678 53 0.0138 54 0.0589 550.00806 56 0.00883 57 0.00358 58 0.00786 59 0.0685 60 0.0749 61 0.030762 0.0697 63 0.012 64 0.0711 65 0.0622 66 0.0822 67 0.0785 68 0.0591 690.0613 70 0.0731 71 0.0107 72 0.0777 73 0.0845 74 0.0153 75 0.0693 760.0224 77 0.0173 78 0.056 79 0.0414 80 0.0632 81 0.0178 82 0.00724 830.00685 84 0.022 85 0.0489 86 0.00548 87 0.00604 88 0.109 89 0.18 900.686 91 0.111 92 0.608 93 0.0876 94 0.598 95 0.0662 96 0.171 97 0.076798 0.0709 99 0.0493 100 0.0273 101 0.0681 102 0.0679 103 0.0981 1040.0951 105 0.0609 106 0.576 107 0.00599 108 0.0815 109 0.11 110 0.0118111 0.0292 112 0.906 113 0.113 114 0.00811 115 0.00611 116 0.135 1170.00983 118 0.0777 119 0.0769 120 0.078 121 0.00773 122 0.00881 1230.00881 124 0.00775 125 0.00812 126 0.00738 127 0.071 128 0.00836 1290.0113 130 0.0787 131 0.00818 132 0.00777 133 0.00443 134 0.0283 1350.00869 136 0.00742 137 0.0516 138 0.00838 139 0.00781 140 0.0263 1410.00833 142 0.00791 143 0.0822 144 0.00904 145 0.0739 146 0.00907 1470.00513 148 0.0167 149 0.0765 150 1.05 151 0.0154 152 0.00604 1530.00803 154 0.00789 155 0.13 156 0.0747 157 0.0378 158 0.0365 159 0.0745160 0.639 161 0.905 162 0.269 163 0.0344 164 0.0259 165 0.0619 1660.0664 167 0.0235 168 0.045 169 0.00798 170 0.0148 171 0.022 172 0.0345173 0.0564 174 0.0244 175 0.0675 176 0.0889 177 0.074 178 0.075 1790.0769 180 0.0677 181 0.0243 182 0.00695 183 0.0633 184 0.0612 1850.00918 186 0.00345 187 0.0863 188 0.00225 189 0.0217 190 0.00583 1910.00746 192 0.0632 193 0.0137 194 0.69 195 0.00866 196 0.0646 197 0.0227198 0.0476 199 nd 200 0.017 201 nd 202 0.0655 203 nd 204 0.0604 205 nd206 0.0634 207 nd 208 0.0737 209 nd 210 0.218 211 nd 212 0.0206 213 nd214 0.0437 215 nd 216 0.0205 217 nd 218 0.188 219 nd 220 0.00415 221 nd222 0.0119 223 nd 224 0.0207 225 nd 226 0.20 227 nd 228 nd 229 nd 230 nd231 0.361 232 nd 233 0.97 234 nd 235 0.993 236 nd 237 0.346 238 0.746239 1.51 240 nd 241 0.252 242 nd 243 1.31 244 nd 245 0.617 246 0.622 2470.471 248 1.38 249 0.541 250 0.664 251 0.212 252 0.401 253 0.622 254 nd255 0.734 256 nd 257 nd 258 0.0683 259 0.0647 260 0.0949 261 0.0713 2620.0516 263 0.365 264 0.0351 265 0.691 266 0.207 267 0.0178 268 0.0228269 0.0167 270 0.0195 271 0.06037 272 0.22243 273 7.27 274 0.0685 2750.0345 276 0.01 277 0.0631 278 0.0306 279 0.0476 280 0.114 281 0.125 2820.0143 283 0.0617 284 0.0223 285 0.0265 286 0.00766 287 0.0374 288 0.084289 0.0352 290 0.0103 291 0.15 292 0.0878 293 0.0705 294 0.0609 2950.0665 296 0.0198 297 0.0182 298 0.0112 299 0.0146 300 0.0171 301 0.0219302 0.141 303 0.0135 304 0.262 305 1.82 306 0.298 307 0.00987 3080.00961 309 0.0111 310 0.00276 311 0.0471 312 0.211 313 4.59 314 0.0839315 0.05416 316 0.0173 317 0.0554 318 0.156 319 0.0307 320 0.155 3210.119 322 0.01251 323 0.051 324 0.00624 325 0.0113 326 0.0165 327 0.189328 0.0527 329 0.0145 330 0.0123 331 0.0424 332 0.0222 333 0.0224 3340.0324 335 0.0158 336 0.222 337 0.0555 338 0.587 339 0.668 340 2.45 3418.94 342 0.39 343 0.831 344 7.67 345 1.13 346 0.843 347 1.55 348 0.803349 0.772 350 0.743 351 0.655 352 0.607 353 nd 354 0.994 355 7.31 3560.791 357 0.703 nd = no data

Compounds which inhibit NAMPT are useful for treating diseases in whichactivation of NF-KB is implicated. Such methods are useful in thetreatment of a variety of diseases including inflammatory and tissuerepair disorders; particularly rheumatoid arthritis, inflammatory boweldisease, asthma and COPD (chronic obstructive pulmonary disease),osteoarthritis, osteoporosis and fibrotic diseases; dermatosis,including psoriasis, atopic dermatitis and ultra-violet induced skindamage; autoimmune diseases including systemic lupus erythematosis,multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissueand organ rejection, Alzheimer's disease, stroke, athersclerosis,restenosis, diabetes, glomerulonephritis, cancer, particularly whereinthe cancer is selected from breast, prostate, lung, colon, cervix,ovary, skin, CNS, bladder, pancreas, leukaemia, lymphoma or Hodgkin'sdisease, cachexia, inflammation associated with infection and certainviral infections, including Acquired Immune Deficiency Syndrome (AIDS),adult respiratory distress syndrome, and ataxia telengiectasia.

Involvement of NAMPT in the treatment of cancer is described in WO97/48696. Involvement of NAMPT in immuno-supression is described in WO97/48397. Involvement of NAMPT for the treatment of diseases involvingangiogenesis is described in WO 2003/80054. Involvement of NAMPT for thetreatment of rheumatoid arthritis and septic shock is described in WO2008/025857. Involvement of NAMPT for the prophlaxis and treatment ofischaemia is described in WO 2009/109610.

Cancers include, but are not limited to, hematologic and solid tumortypes such as acoustic neuroma, acute leukemia, acute lymphoblasticleukemia, acute myelogenous leukemia (monocytic, myeloblastic,adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic andpromyelocytic), acute t-cell leukemia, basal cell carcinoma, bile ductcarcinoma, bladder cancer, brain cancer, breast cancer (includingestrogen-receptor positive breast cancer), bronchogenic carcinoma,Burkitt's lymphoma, cervical cancer, chondrosarcoma, chordoma,choriocarcinoma, chronic leukemia, chronic lymphocytic leukemia, chronicmyelocytic (granulocytic) leukemia, chronic myelogenous leukemia, coloncancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma,dysproliferative changes (dysplasias and metaplasias), embryonalcarcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelialcarcinoma, erythroleukemia, esophageal cancer, estrogen-receptorpositive breast cancer, essential thrombocythemia, Ewing's tumor,fibrosarcoma, gastric carcinoma, germ cell testicular cancer,gestational trophobalstic disease, glioblastoma, head and neck cancer,heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer,hormone insensitive prostate cancer, leiomyosarcoma, liposarcoma, lungcancer (including small cell lung cancer and non-small cell lungcancer), lymphangioendothelio-sarcoma, lymphangiosarcoma, lymphoblasticleukemia, lymphoma (lymphoma, including diffuse large B-cell lymphoma,follicular lymphoma, Hodgkin's lymphoma and non-Hodgkin's lymphoma),malignancies and hyperproliferative disorders of the bladder, breast,colon, lung, ovaries, pancreas, prostate, skin and uterus, lymphoidmalignancies of T-cell or B-cell origin, leukemia, medullary carcinoma,medulloblastoma, melanoma, meningioma, mesothelioma, multiple myeloma,myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma,oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer,pancreatic cancer, papillary adenocarcinomas, papillary carcinoma,peripheral T-cell lymphoma, pinealoma, polycythemia vera, prostatecancer (including hormone-insensitive (refractory) prostate cancer),rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma,sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small celllung carcinoma, solid tumors (carcinomas and sarcomas), stomach cancer,squamous cell carcinoma, synovioma, sweat gland carcinoma, testicularcancer (including germ cell testicular cancer), thyroid cancer,Waldenstrm's macroglobulinemia, testicular tumors, uterine cancer,Wilms' tumor and the like.

Schemes and Experimentals

The following abbreviations have the meanings indicated. ADDP means1,1′-(azodicarbonyl)dipiperidine; AD-mix-β means a mixture of(DHQD)₂PHAL, K₃Fe(CN)₆, K₂CO₃, and K₂SO₄; 9-BBN means9-borabicyclo(3.3.1)nonane; Boc means tert-butoxycarbonyl; (DHQD)₂PHALmeans hydroquinidine 1,4-phthalazinediyl diethyl ether; DBU means1,8-diazabicyclo[5.4.0]undec-7-ene; DIBAL means diisobutylaluminumhydride; DIEA means diisopropylethylamine; DMAP meansN,N-dimethylaminopyridine; DMF means N,N-dimethylformamide; dmpe means1,2-bis(dimethylphosphino)ethane; DMSO means dimethylsulfoxide; dppbmeans 1,4-bis(diphenylphosphino)-butane; dppe means1,2-bis(diphenylphosphino)ethane; dppf means1,1′-bis(diphenylphosphino)ferrocene; dppm means1,1-bis(diphenylphosphino)methane; EDAC.HCl means1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; Fmoc meansfluorenylmethoxycarbonyl; HATU meansO-(7-azabenzotriazol-1-yl)-N,N′N′N′-tetramethyluroniumhexafluorophosphate; HMPA means hexamethylphosphoramide; IPA meansisopropyl alcohol; MP-BH₃ means macroporous triethylammoniummethylpolystyrene cyanoborohydride; TEA means triethylamine; TFA meanstrifluoroacetic acid; THF means tetrahydrofuran; NCS meansN-chlorosuccinimide; NMM means N-methylmorpholine; NMP meansN-methylpyrrolidine; PPh₃ means triphenylphosphine.

The following schemes are presented to provide what is believed to bethe most useful and readily understood description of procedures andconceptual aspects of this invention. Compounds of this invention may bemade by synthetic chemical processes, examples of which are shownherein. It is meant to be understood that the order of the steps in theprocesses may be varied, that reagents, solvents and reaction conditionsmay be substituted for those specifically mentioned, and that vulnerablemoieties may be protected and deprotected, as necessary.

Schemes

As shown in Scheme 1, compounds of formula (1), wherein X¹, X², and R¹are as described in Formula (I), n is 1 or 2, m is 1 or 2, and X is CHwhen n is 1 or 2 and m is 1, and X is N or CH when n is 2 and m is 2,can be reacted with compounds of formula (2), wherein R² is as describedherein, in the presence of bis(2,5-dioxopyrrolidin-1-yl) carbonate and abase such as but not limited to diisopropylethylamine to providecompounds of formula (3). The reaction is typically performed at ambienttemperature in a solvent such as but not limited to acetonitrile.

tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylate can be reacted canbe reacted with compounds of formula (1), wherein X¹, X², and R¹ are asdescribed in Formula (I), n is 1 or 2, m is 1 or 2, and X is CH when nis 1 or 2 and m is 1, and X is N or CH when n is 2 and m is 2, in thepresence of bis(2,5-dioxopyrrolidin-1-yl) carbonate and a base such asbut not limited to diisopropylethylamine to provide compounds of formula(4). The reaction is typically performed at ambient temperature in asolvent such as but not limited to acetonitrile. Compounds of formula(5) can be prepared by treating compounds of formula (4) with an acidsuch as but not limited to trifluoroacetic acid in a solvent such as butnot limited to dichloromethane. Compounds of formula (7), which arerepresentative of compounds of Formula (I), can be prepared by reactingcompounds of formula (5) with compounds of formula (6), wherein R¹⁰ isas described herein, in the presence of a base such as but not limitedto diisopropylethylamine. The reaction may involve the use of a carboxylactivating agent such as but not limited toN-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and aester activating agent such as but not limited to 1-hydroxybenzotriazolehydrate. The reaction is typically performed at ambient temperature in asolvent such as but not limited to N,N-dimethylformamide,N,N-dimethylacetamide, or mixtures thereof. Alternatively, compounds offormula (5) can be reacted with compounds of formula (8), wherein R¹⁰ isas described herein, to provide compounds of formula (9), which arerepresentative of compounds of Formula (I). The reaction is typicallyperformed in the presence of a reducing agent such as but not limited tosodium triacetoxyborohydride and acetic acid in a solvent such as butnot limited to methanol and may be performed at an elevated temperature.

As shown in Scheme 3, tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate, can be reacted can be reactedwith compounds of formula (1), wherein X¹, X², and R¹ are as describedin Formula (I), n is 1 or 2, m is 1 or 2, and X is CH when n is 1 or 2and m is 1, and X is N or CH when n is 2 and m is 2, in the presence ofbis(2,5-dioxopyrrolidin-1-yl) carbonate and a base such as but notlimited to diisopropylethylamine to provide compounds of formula (10).The reaction is typically performed at ambient temperature in a solventsuch as but not limited to acetonitrile. Compounds of formula (11) canbe prepared by treating compounds of formula (10) with an acid such asbut not limited to trifluoroacetic acid in a solvent such as but notlimited to dichloromethane. Compounds of formula (12), which arerepresentative of compounds of Formula (I), can be prepared by reactingcompounds of formula (11) with compounds of formula (6), wherein R¹⁰ isas described herein, in the presence of a base such as but not limitedto diisopropylethylamine. The reaction may involve the use of a carboxylactivating agent such as but not limited toN-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, and aester activating agent such as but not limited to 1-hydroxybenzotriazolehydrate. The reaction is typically performed at ambient temperature in asolvent such as but not limited to N,N-dimethylformamide,N,N-dimethylacetamide, or mixtures thereof.

EXAMPLES

The following examples are presented to provide what is believed to bethe most useful and readily understood description of procedures andconceptual aspects of this invention. Each exemplified compound andintermediate was named using ACD/ChemSketch Version 12.5 (20 Apr. 2011),Advanced Chemistry Development Inc., Toronto, Ontario), or ChemDraw®Ver. 9.0.7 (CambridgeSoft, Cambridge, Mass.).

Experimentals Example 1N-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamideExample 1A tert-butyl 3-(4-nitrophenoxy)azetidine-1-carboxylate

Tert-butyl 3-hydroxyazetidine-1-carboxylate (4.0 g, 23.3 mmol),1-fluoro-4-nitrobenzene (6.1 g, 43.0 mmol), aqueous potassium hydroxide(35.5 ml of a 5.9 M solution, 209 mmol), and tetrabutylammonium bromide(0.975 g, 3.0 mmol) were combined and stirred at 40° C. overnight. Thereaction was cooled, diluted with water and extracted three times withethyl acetate. The combined organics were dried (sodium sulfate),filtered and concentrated. The residue was purified by regular phaseflash column chromatography to give the title compound.

Example 1B tert-butyl 3-(4-aminophenoxy)azetidine-1-carboxylate

Tert-butyl 3-(4-nitrophenoxy)azetidine-1-carboxylate (1 g, 3.40 mmol)and tetrahydrofuran (20 ml) were added to 5% palladium on carbon (wet,0.200 g, 1.879 mmol) in a 250 mL SS pressure bottle and the mixture wasstirred for 1 hour at 30 psi and room temperature. The mixture wasfiltered through a nylon membrane and the fitrate was concentrated togive the title compound.

Example 1C tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate

Tert-butyl 3-(4-aminophenoxy)azetidine-1-carboxylate (1.17 g, 4.43 mmol)and bis(2,5-dioxopyrrolidin-1-yl) carbonate (1.134 g, 4.43 mmol) werecombined in acetonitrile (22.13 ml) and stirred for 1 hour at roomtemperature. 3-(Azetidin-3-yl)pyridine bis hydrochloride (0.948 g, 4.65mmol) and diisopropylethylamine (3.09 ml, 17.71 mmol) were added and thereaction mixture was stirred overnight. The acetonitrile was removed byrotary evaporation and the residue was taken up in dichloromethane andchromatographed using regular phase chromatography to give the titlecompound.

Example 1DN-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

To a 20 mL vial was added tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate (800 mg, 1.885 mmol) in dichloromethane (9.42mL). Trifluoroacetic acid (1.4 mL, 18.17 mmol) was added and thereaction mixture was stirred at room temperature for 1.5 hours. Thevolatiles were removed under vacuum to give the title compound.

Example 1E(S)—N-(4-(1-(2-methylbutanoyl)azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

N-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide(1 g, 1.805 mmol), (S)-2-methylbutanoic acid (0.221 g, 2.166 mmol), andN-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.519 g,2.71 mmol) were combined in in dimethylformamide (9.03 mL) at roomtemperature. 1-Hydroxybenzotriazole hydrate (0.415 g, 2.71 mmol) anddiisopropylethylamine (0.946 ml, 5.42 mmol) were added and the reactionmixture was stirred overnight at room temperature. Water anddichloromethane were added and the organics were removed by pipet.Concentration and reverse phase chromatography gave(S)—N-(4-(1-(2-methylbutanoyl)azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide.¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J=2.4 Hz, 1H), 8.48 (dd, J=4.7, 1.6Hz, 1H), 8.41 (s, 1H), 7.86 (dt, J=7.9, 2.0 Hz, 1H), 7.46-7.37 (m, 3H),6.76 (d, J=8.9 Hz, 2H), 4.96 (dd, J=6.3, 3.4 Hz, 1H), 4.62-4.53 (m, 1H),4.36 (d, J=15.9 Hz, 2H), 4.32-4.22 (m, 1H), 4.11-4.02 (m, 1H), 3.98-3.81(m, 3H), 3.75 (dd, J=10.6, 3.9 Hz, 1H), 2.36-2.20 (m, 1H), 1.59-1.39 (m,1H), 1.38-1.20 (m, 1H), 0.96 (dd, J=6.8, 3.9 Hz, 3H), 0.82 (q, J=7.2 Hz,3H); MS (ESI(+)) m/e 409 (M+H)¹¹.

TABLE 1 The following Examples were prepared essentially as described inExample 1, substituting the appropriate alcohol in Example 1A, theappropriate amine in Example 1C and the appropriate carboxylic acid inExample 1E. Some products were purified by flash chromatography whileothers were purified by reverse-phase HPLC. Accordingly, some Exampleswere isolated as trifluoroacetic acid salts. Ex Name ¹H NMR MS 23-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆) δ (ESI(+))(4-{[1-(tetrahydro- 8.62-8.44 (m, 2H), 8.36 (s, 1H), 7.94-7.78 (m, m/e479 2H-pyran-4- 1H), 7.49-7.31 (m, 3H), 6.96-6.80 (m, (M + H)⁺ylacetyl)piperidin-4- 2H), 4.58-4.25 (m, 3H), 4.02-3.64 (m,yl]oxy}phenyl)azetidine- 7H), 3.64-3.53 (m, 1H), 3.09-2.85 (m,1-carboxamide 1H), 2.84-2.68 (m, 1H), 2.30-2.25 (m, 2H), 2.21-2.13 (m,1H), 2.00-1.79 (m, 3H), 1.66-1.35 (m, 4H), 1.32-1.11 (m, 2H) 33-(5-fluoropyridin-3- ¹H NMR (300 MHz, DMSO-d₆) δ 8.49 (d, J = 2.8 Hz,(ESI(+)) yl)-N-(4-{[1- 1H), 8.46 (t, J = 1.8 Hz, 1H), m/e 497(tetrahydro-2H- 8.37 (s, 1H), 7.89-7.80 (m, 1H), 7.43-7.36 (m, (M + H)⁺pyran-4- 2H), 6.91-6.84 (m, 2H), 4.55-4.43 (m, ylacetyl)piperidin-4-1H), 4.39-4.28 (m, 2H), 4.05-3.63 (m, yl]oxy}phenyl)azetidine- 7H),3.25-3.14 (m, 2H), 2.27 (d, J = 1.4 Hz, 1-carboxamide 1H), 2.00-1.77 (m,3H), 1.66-1.33 (m, 4H), 1.32-1.04 (m, 2H) 4 N-[4-({1-[(2S)-2- ¹H NMR(300 MHz, DMSO-d₆) δ (ESI(+)) methylbutanoyl]piperidin- 8.59-8.46 (m,2H), 8.36 (s, 1H), 7.86 (dt, J = 7.9, m/e 437 4- 2.0 Hz, 1H), 7.45-7.35(m, 3H), (M + H)⁺ yl}oxy)phenyl]-3- 6.92-6.85 (m, 2H), 4.51 (dq, J =7.8, 3.9 Hz, 1H), (pyridin-3- 4.36 (d, J = 15.9 Hz, 2H), 4.03-3.70 (m,yl)azetidine-1- 5H), 2.72 (h, J = 6.7 Hz, 1H), carboxamide 1.99-1.79 (m,2H), 1.64-1.36 (m, 3H), 1.38-1.18 (m, 1H), 0.98 (d, J = 6.7 Hz, 3H),0.80 (d, J = 7.3 Hz, 2H) 5 3-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆)δ 8.56 (d, J = 2.4 Hz, (ESI(+)) [4-({1-[(2R)- 1H), 8.48 (dd, J = 4.7,1.6 Hz, m/e 451 tetrahydrofuran-2- 1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9,2.0 Hz, (M + H)⁺ ylcarbonyl]piperidin- 1H), 7.45-7.35 (m, 3H), 6.92-6.85(m, 4- 2H), 4.67 (t, J = 6.6 Hz, 1H), yl}oxy)phenyl]azetidine- 4.56-4.44(m, 1H), 4.36 (t, J = 8.1 Hz, 1H), 1-carboxamide 3.99-3.66 (m, 7H),2.11-1.69 (m, 6H), 1.64-1.38 (m, 2H) 6 3-(pyridin-3-yl)-N- ¹H NMR (300MHz, DMSO-d₆) δ (ESI(+)) (4-{[1-(3,3,3- 8.59-8.45 (m, 2H), 8.37 (s, 1H),7.86 (dt, J = 7.9, m/e 463 trifluoropropanoyl)piperidin- 2.0 Hz, 1H),7.45-7.35 (m, 3H), (M + H)⁺ 4- 6.92-6.85 (m, 2H), 4.58-4.42 (m, 1H),4.36 (t, J = 8.1 Hz, yl]oxy}phenyl)azetidine- 1H), 4.01-3.74 (m, 4H),3.66 (q, 1-carboxamide J = 11.0 Hz, 3H), 2.00-1.78 (m, 2H), 1.70-1.41(m, 2H) 7 N-(4-{[1-(2-hydroxy- ¹H NMR (300 MHz, DMSO-d₆) δ (ESI(+)) 2-16.84-16.76 (m, 1H), 8.56 (d, J = 2.3 Hz, 1H), m/e 439methylpropanoyl)piperidin- 8.48 (dd, J = 4.7, 1.6 Hz, 1H), 8.37 (s, 1H),(M + H)⁺ 4- 7.86 (dt, J = 7.9, 2.0 Hz, 1H), yl]oxy}phenyl)-3- 7.45-7.35(m, 3H), 6.91-6.84 (m, 2H), 5.39 (s, 1H), (pyridin-3- 4.55-4.43 (m, 1H),4.36 (d, J = 15.9 Hz, yl)azetidine-1- 2H), 4.02 (bs, 1H), 4.02-3.76 (m,4H), carboxamide 1.96-1.85 (m, 2H), 1.61-1.40 (m, 2H), 1.31 (s, 6H) 83-(6-methylpyridin-3- ¹H NMR (300 MHz, DMSO-d₆) δ 8.41 (d, J = 2.4 Hz,(ESI(+)) yl)-N-(4-{[1- 1H), 8.35 (s, 1H), 7.75 (dd, J = 8.0, m/e 493(tetrahydro-2H- 2.4 Hz, 1H), 7.42-7.35 (m, 2H), (M + H)⁺ pyran-4- 7.27(d, J = 8.0 Hz, 1H), 6.94-6.84 (m, 2H), ylacetyl)piperidin-4- 4.58-4.43(m, 1H), 4.33 (t, J = 8.1 Hz, yl]oxy}phenyl)azetidine- 2H), 3.99-3.57(m, 9H), 2.45 (s, 1H), 1-carboxamide 2.27 (d, J = 1.5 Hz, 1H), 2.05-1.79(m, 4H), 1.66-1.38 (m, 5H), 1.31-1.10 (m, 3H) 28 3-(pyridin-3-yl)-N- ¹HNMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.3 Hz, (ESI(+)) [4-({1-[(2R)-1H), 8.48 (dd, J = 4.8, 1.6 Hz, m/e 423 tetrahydrofuran-2- 1H), 8.40 (s,1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M + H)⁺ ylcarbonyl]azetidin- 1H),7.45-7.37 (m, 3H), 6.79-6.72 (m, 3- 2H), 5.02-4.91 (m, 1H), 4.73-4.60(m, yl}oxy)phenyl]azetidine- 1H), 4.43-4.24 (m, 4H), 4.20-4.07 (m,1-carboxamide 1H), 4.09-3.63 (m, 6H), 2.16-1.70 (m, 4H) 293-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.4 Hz,(ESI(+)) [4-({1-[(2S)- 1H), 8.51-8.39 (m, 2H), 8.40 (s, m/e 423tetrahydrofuran-2- 1H), 7.86 (dt, J = 7.9, 2.0 Hz, 1H), (M + H)⁺ylcarbonyl]azetidin- 7.62-7.37 (m, 3H), 6.79-6.72 (m, 2H), 3- 5.02-4.91(m, 1H), 4.73-4.60 (m, 1H), yl}oxy)phenyl]azetidine- 4.42-4.25 (m, 4H),4.19-4.09 (m, 1H), 1-carboxamide 4.02-3.63 (m, 6H), 2.14-1.70 (m, 4H) 30N-(4-{[1-(2-hydroxy- ¹H NMR (300 MHz, DMSO-d₆) δ (ESI(+)) 2- 8.58-8.45(m, 1H), 8.40 (s, 1H), 7.86 (dt, J = 7.9, m/e 411methylpropanoyl)azetidin- 2.0 Hz, 1H), 7.45-7.35 (m, 3H), (M + H)⁺ 3-6.78-6.71 (m, 2H), 5.13 (s, 1H), 5.00-4.73 (m, yl]oxy}phenyl)-3- 2H),4.36 (d, J = 15.9 Hz, 2H), (pyridin-3- 4.29-4.22 (m, 2H), 3.98-3.85 (m,3H), yl)azetidine-1- 3.78-3.69 (m, 1H), 1.25 (s, 6H) carboxamide 313-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.3 Hz,(ESI(+)) [4-({1-[(2S)- 1H), 8.48 (dd, J = 4.7, 1.6 Hz, m/e 451tetrahydrofuran-2- 1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M +H)⁺ ylcarbonyl]piperidin- 1H), 7.45-7.29 (m, 3H), 6.92-6.85 (m, 4- 2H),4.67 (t, J = 6.6 Hz, 1H), 4.50 (d, J = 3.1 Hz, yl}oxy)phenyl]azetidine-1H), 4.36 (d, J = 15.9 Hz, 2H), 1-carboxamide 4.01-3.67 (m, 7H),2.11-1.68 (m, 6H), 1.65-1.33 (m, 2H) 32 3-(pyridin-3-yl)-N- ¹H NMR (300MHz, DMSO-d₆) δ 8.56 (d, J = 2.2 Hz, (ESI(+)) (4-{[1-(thiophen-2- 1H),8.59-8.45 (m, 2H), 8.38 (s, m/e 463 ylcarbonyl)piperidin- 1H), 7.86 (dt,J = 7.9, 2.0 Hz, 1H), (M + H)⁺ 4- 7.80-7.69 (m, 1H), 7.45-7.36 (m, 4H),yl]oxy}phenyl)azetidine- 7.12 (ddd, J = 5.0, 3.6, 0.5 Hz, 1H),1-carboxamide 6.94-6.87 (m, 2H), 4.57 (dq, J = 7.6, 3.8 Hz, 1H), 4.36(d, J = 15.9 Hz, 2H), 3.99-3.80 (m, 5H), 3.58-3.42 (m, 2H), 2.06-1.84(m, 2H), 1.73-1.54 (m, 2H) 33 3-(pyridin-3-yl)-N- ¹H NMR (300 MHz,DMSO-d₆) δ 8.56 (d, J = 2.1 Hz, (ESI(+)) (4-{[1-(thiophen-3- 1H),8.59-8.45 (m, 2H), 8.38 (s, m/e 463 ylcarbonyl)piperidin- 1H), 7.86 (dt,J = 7.9, 2.0 Hz, 1H), 7.79 (dd, (M + H)⁺ 4- J = 2.9, 1.3 Hz, 1H), 7.61(dd, J = 4.9, 2.9 Hz, yl]oxy}phenyl)azetidine- 1H), 7.45-7.35 (m, 3H),7.21 (dd, J = 4.9, 1-carboxamide 1.3 Hz, 1H), 6.93-6.86 (m, 2H), 4.53(dq, J = 7.8, 3.9 Hz, 1H), 4.36 (d, J = 15.9 Hz, 2H), 4.02-3.66 (m, 5H),3.49-3.34 (m, 1H), 1.99-1.86 (m, 2H), 1.72-1.52 (m, 2H) 34 N-[4-({1-[(1-¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.2 Hz, (ESI(+))acetylpiperidin-4- 1H), 8.59-8.45 (m, 2H), 8.37 (s, m/e 506yl)carbonyl]piperidin- 1H), 7.86 (dt, J = 7.9, 2.0 Hz, 1H), (M + H)⁺4-yl}oxy)phenyl]-3- 7.45-7.35 (m, 3H), 6.92-6.85 (m, 2H), (pyridin-3-4.56-4.42 (m, 1H), 4.36 (t, J = 7.9 Hz, 3H), yl)azetidine-1- 4.02-3.71(m, 6H), 3.15-3.02 (m, 1H), carboxamide 2.98-2.84 (m, 1H), 2.58 (dd, J =22.3, 12.2 Hz, 1H), 1.98 (s, 3H), 1.69-1.24 (m, 6H) 35 N-[4-({1-[(2- ¹HNMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.0 Hz, (ESI(+))methylcyclopropyl)carbonyl]piperidin- 1H), 8.59-8.46 (m, 2H), 8.36 (s,m/e 435 4- 1H), 7.86 (dt, J = 7.9, 2.0 Hz, 1H), (M + H)⁺yl}oxy)phenyl]-3- 7.45-7.36 (m, 3H), 6.92-6.85 (m, 2H), (pyridin-3-4.56-4.45 (m, 1H), 4.36 (d, J = 15.9 Hz, 2H), yl)azetidine-1- 4.03-3.76(m, 6H), 3.48 (bs, 1H), carboxamide 2.03-1.77 (m, 2H), 1.77-1.67 (m,1H), 1.49 (bs, 2H), 1.16-1.03 (m, 4H), 1.07 (s, 3H), 0.97-0.83 (m, 1H),0.57-0.49 (m, 1H) 36 N-[4-({1-[(1-methyl- ¹H NMR (300 MHz, DMSO-d₆) δ8.56 (d, J = 2.3 Hz, (ESI(+)) 1H-pyrrol-2- 1H), 8.48 (dd, J = 4.7, 1.6Hz, m/e 460 yl)carbonyl]piperidin- 1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9,2.0 Hz, (M + H)⁺ 4-yl}oxy)phenyl]-3- 1H), 7.45-7.36 (m, 3H), 6.93-6.85(m, (pyridin-3- 3H), 6.31 (dd, J = 3.7, 1.7 Hz, 1H), yl)azetidine-1-6.02 (dd, J = 3.7, 2.5 Hz, 1H), 4.54 (p, J = 3.8 Hz, carboxamide 1H),4.36 (d, J = 15.9 Hz, 2H), 4.00-3.78 (m, 5H), 3.66 (s, 3H), 3.52-3.41(m, 2H), 2.03-1.85 (m, 2H), 1.70-1.49 (m, 2H) 37 N-[4-({1-[3- ¹H NMR(300 MHz, DMSO-d₆) δ 8.57 (dd, (ESI(+)) (morpholin-4- J = 6.8, 1.7 Hz,1H), 8.52-8.42 (m, 1H), m/e 518 yl)propanoyl]piperidin- 8.37 (s, 1H),7.86 (dt, J = 7.9, 2.0 Hz, 1H), (M + H)⁺ 4-yl}oxy)phenyl]- 7.45-7.29 (m,3H), 6.91-6.84 (m, 2H), 3-(pyridin-3- 4.55-4.40 (m, 1H), 4.36 (d, J =15.9 Hz, yl)azetidine-1- 2H), 3.98-3.77 (m, 4H), 3.75-3.65 (m,carboxamide 1H), 3.59-3.52 (m, 4H), 2.41-2.34 (m, 4H), 2.03-1.74 (m,1H), 1.67-1.37 (m, 2H) 38 N-[4-({1-[3-(4- ¹H NMR (300 MHz, DMSO-d₆) δ8.56 (d, J = 2.4 Hz, (ESI(+)) methylpiperazin-1- 1H), 8.48 (dd, J = 4.7,1.6 Hz, m/e 505 yl)propanoyl]piperidin- 1H), 8.37 (s, 1H), 7.94-7.82 (m,1H), (M + H)⁺ 4-yl}oxy)phenyl]- 7.49-7.20 (m, 4H), 6.91-6.84 (m, 2H),3-(pyridin-3- 4.55-4.40 (m, 1H), 4.36 (d, J = 15.9 Hz, 2H),yl)azetidine-1- 3.98-3.77 (m, 5H), 3.75-3.66 (m, 1H), carboxamide2.37-2.18 (m, 5H), 1.91 (s, 1H), 1.65-1.34 (m, 1H) 393-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.3 Hz,(ESI(+)) [4-({1-[3-(pyrrolidin- 1H), 8.48 (dd, J = 4.8, 1.6 Hz, m/e 4781- 1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M + H)⁺yl)propanoyl]piperidin- 1H), 7.49-7.33 (m, 4H), 6.93-6.81 (m, 4- 3H),4.54-4.28 (m, 4H), 3.98-3.64 (m, yl}oxy)phenyl]azetidine- 7H), 2.71-2.62(m, 2H), 1.98-1.79 (m, 1-carboxamide 3H), 1.75-1.61 (m, 5H), 1.62-1.39(m, 3H) 40 N-(4-{[1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.1 Hz,(ESI(+)) (cyclopropylacetyl)piperidin- 1H), 8.48 (dd, J = 4.8, 1.6 Hz,m/e 435 4- 1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M + H)⁺yl]oxy}phenyl)-3- 1H), 7.45-7.35 (m, 3H), 6.91-6.84 (m, (pyridin-3- 2H),4.55-4.43 (m, 1H), 4.36 (d, J = 15.9 Hz, yl)azetidine-1- 2H), 3.98-3.79(m, 4H), carboxamide 3.76-3.59 (m, 1H), 3.25-3.15 (m, 1H), 2.27 (d, J =6.7 Hz, 2H), 1.98-1.80 (m, 2H), 1.63-1.36 (m, 2H), 1.07-0.86 (m, 1H),0.49-0.35 (m, 2H), 0.20-0.07 (m, 2H) 41 N-(4-{[1-(3- ¹H NMR (300 MHz,DMSO-d₆) δ 8.56 (d, J = 2.2 Hz, (ESI(+)) methylpentanoyl)piperidin- 1H),8.48 (dd, J = 4.7, 1.6 Hz, m/e 451 4- 1H), 8.37 (s, 1H), 7.86 (dt, J =7.9, 2.0 Hz, (M + H)⁺ yl]oxy}phenyl)-3- 1H), 7.45-7.35 (m, 3H),6.91-6.84 (m, (pyridin-3- 2H), 4.49 (dq, J = 7.8, 3.9 Hz, 1H), 4.36 (d,yl)azetidine-1- J = 15.9 Hz, 2H), 3.98-3.80 (m, 4H), carboxamide3.77-3.65 (m, 1H), 3.28-3.13 (m, 1H), 2.30 (dt, J = 14.9, 5.4 Hz, 1H),2.19-2.06 (m, 1H), 2.01-1.68 (m, 1H), 1.48 (ddd, J = 24.8, 16.8, 10.2Hz, 1H), 1.34 (ddd, J = 14.9, 10.2, 6.5 Hz, 1H), 1.14 (tq, J = 14.4, 7.3Hz, 1H), 0.90-0.73 (m, 6H) 42 N-(4-{[1-(4- ¹H NMR (300 MHz, DMSO-d₆) δ8.56 (d, J = 2.2 Hz, (ESI(+)) methylpentanoyl)piperidin- 1H), 8.48 (dd,J = 4.7, 1.5 Hz, m/e 451 4- 1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9, 2.0Hz, (M + H)⁺ yl]oxy}phenyl)-3- 1H), 7.48-7.34 (m, 3H), 6.91-6.84 (m,(pyridin-3- 2H), 4.49 (dq, J = 7.8, 3.9 Hz, 1H), 4.36 (d,yl)azetidine-1- J = 15.9 Hz, 2H), 3.98-3.77 (m, 4H), carboxamide3.76-3.63 (m, 1H), 3.25-3.03 (m, 2H), 2.35-2.26 (m, 2H), 1.98-1.77 (m,2H), 1.64-1.28 (m, 5H), 0.87 (d, J = 6.5 Hz, 6H) 43 N-{4-[(1- ¹H NMR(300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.0 Hz, (ESI(+)) butanoylpiperidin-4-1H), 8.48 (dd, J = 4.8, 1.6 Hz, m/e 423 yl)oxy]phenyl}-3- 1H), 8.36 (s,1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M + H)⁺ (pyridin-3- 1H), 7.45-7.35 (m,3H), 6.91-6.84 (m, yl)azetidine-1- 2H), 4.54-4.43 (m, 1H), 4.36 (d, J =15.9 Hz, carboxamide 2H), 4.02-3.78 (m, 4H), 3.75-3.62 (m, 1H),3.27-3.07 (m, 1H), 2.29 (t, J = 7.3 Hz, 2H), 1.97-1.80 (m, 2H),1.63-1.38 (m, 4H), 0.91 (s, 1H), 0.88 (d, J = 7.4 Hz, 2H) 44N-(4-{[1-(2,2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.0 Hz, (ESI(+))dimethylpropanoyl)piperidin- 1H), 8.48 (dd, J = 4.8, 1.6 Hz, m/e 437 4-1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M + H)⁺ yl]oxy}phenyl)-3-1H), 7.45-7.35 (m, 3H), 6.91-6.84 (m, (pyridin-3- 2H), 4.56-4.45 (m,1H), 4.36 (d, J = 15.9 Hz, yl)azetidine-1- 2H), 3.99-3.77 (m, 5H),carboxamide 1.99-1.83 (m, 2H), 1.62-1.35 (m, 2H), 1.20 (s, 9H) 45N-(4-{[1-(3,3- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.0 Hz, (ESI(+))dimethylbutanoyl)piperidin- 1H), 8.48 (dd, J = 4.8, 1.6 Hz, m/e 451 4-1H), 8.36 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M + H)⁺ yl]oxy}phenyl)-3-1H), 7.45-7.35 (m, 3H), 6.91-6.84 (m, (pyridin-3- 2H), 4.54-4.42 (m,1H), 4.36 (d, J = 15.9 Hz, yl)azetidine-1- 2H), 4.02-3.70 (m, 5H), 2.24(s, 2H), carboxamide 1.98-1.81 (m, 2H), 1.62-1.39 (m, 2H), 0.99 (s, 9H)46 N-(4-{[1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.1 Hz, (ESI(+))(ethoxyacetyl)piperidin- 1H), 8.48 (dd, J = 4.8, 1.6 Hz, m/e 4394-yl]oxy}phenyl)- 1H), 8.37 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz, (M + H)⁺3-(pyridin-3- 1H), 7.45-7.35 (m, 3H), 6.92-6.85 (m, yl)azetidine-1- 2H),4.55-4.44 (m, 1H), 4.36 (d, J = 15.9 Hz, carboxamide 2H), 4.11 (d, J =1.3 Hz, 2H), 3.98-3.74 (m, 4H), 3.72-3.59 (m, 1H), 3.46 (q, J = 7.0 Hz,2H), 1.94-1.83 (m, 2H), 1.65-1.40 (m, 2H), 1.13 (t, J = 7.0 Hz, 3H) 47N-(4-{[1- ¹H NMR (300 MHz, DMSO-d₆) δ (ESI(+))(cyclopropylcarbonyl)piperidin- 8.58-8.45 (m, 2H), 8.36 (s, 1H), 7.86(dt, J = 7.9, m/e 421 4- 2.0 Hz, 1H), 7.44-7.35 (m, 3H), (M + H)⁺yl]oxy}phenyl)-3- 6.92-6.85 (m, 2H), 4.57-4.45 (m, 1H), 4.36 (d,(pyridin-3- J = 15.9 Hz, 2H), 4.02-3.76 (m, 5H), yl)azetidine-1-3.58-3.38 (m, 1H), 3.28-3.08 (m, 1H), carboxamide 2.05-1.79 (m, 3H),1.49 (bs, 2H), 0.77-0.63 (m, 4H) 48 N-(4-{[1- ¹H NMR (300 MHz, DMSO-d₆)δ 8.56 (d, J = 2.2 Hz, (ESI(+)) (methoxyacetyl)piperidin- 1H), 8.48 (dd,J = 4.7, 1.6 Hz, m/e 425 4- 1H), 8.37 (s, 1H), 7.94-7.78 (m, 1H), (M +H)⁺ yl]oxy}phenyl)-3- 7.49-7.31 (m, 3H), 6.96-6.81 (m, 2H), (pyridin-3-4.59-4.44 (m, 1H), 4.35 (t, J = 8.0 Hz, 1H), yl)azetidine-1- 4.09 (s,2H), 4.01-3.73 (m, 4H), 3.57 (d, J = 12.9 Hz, carboxamide 1H), 3.28 (s,2H), 3.22 (d, J = 19.7 Hz, 1H), 1.90 (s, 2H), 1.50 (s, 2H) 763-(pyridin-3-yl)-N- (ESI(+)) (4-{[(3R)-1- m/e 465 (tetrahydro-2H- (M +H)⁺ pyran-4- ylacetyl)pyrrolidin-3- yl]oxy}phenyl)azetidine-1-carboxamide 77 N-(4-{[(3R)-1-(2- (ESI(+)) methylpropanoyl)pyrrolidin-m/e 409 3- (M + H)⁺ yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1-carboxamide 78 3-(pyridin-3-yl)-N- (ESI(+)) [4-({(3R)-1-[(2S)- m/e 437tetrahydrofuran-2- (M + H)⁺ ylcarbonyl]pyrrolidin- 3-yl}oxy)phenyl]azetidine- 1-carboxamide 79 3-(pyridin-3-yl)-N- (ESI(+))[4-({(3R)-1-[(2R)- m/e 437 tetrahydrofuran-2- (M + H)⁺ylcarbonyl]pyrrolidin- 3- yl}oxy)phenyl]azetidine- 1-carboxamide 803-(pyridin-3-yl)-N- (ESI(+)) (4-{[(3R)-1- m/e 437 (tetrahydrofuran-3-(M + H)⁺ ylcarbonyl)pyrrolidin- 3- yl]oxy}phenyl)azetidine-1-carboxamide 81 N-(4-{[(3R)-1- (ESI(+)) (cyclopropylacetyl)pyrrolidin-m/e 421 3- (M + H)⁺ yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1-carboxamide 82 N-(4-{[(3R)-1-(2- (ESI(+)) hydroxy-2- m/e 424methylpropanoyl)pyrrolidin- (M + H)⁺ 3- yl]oxy}phenyl)-3- (pyridin-3-yl)azetidine-1- carboxamide 83 N-(4-{[(3R)-1- (ESI(+))benzoylpyrrolidin-3- m/e 443 yl]oxy}phenyl)-3- (M + H)⁺ (pyridin-3-yl)azetidine-1- carboxamide 84 3-(pyridin-3-yl)-N- ¹H NMR (400 MHz,DMSO-d₆/D₂O, Temp = 90° C.) (ESI(+)) (4-{[(3R)-1-(3,3,3- δ 8.73 (d, J =2.1 Hz, 1H), 8.64 (d, m/e 449 trifluoropropanoyl)pyrrolidin- J = 4.4 Hz,1H), 8.33-8.26 (m, 1H), (M + H)⁺ 3- 7.83-7.76 (m, 1H), 7.42-7.35 (m,2H), yl]oxy}phenyl)azetidine- 6.89-6.81 (m, 2H), 5.01-4.90 (m, 1H),1-carboxamide 4.47-4.37 (m, 2H), 4.08-3.96 (m, 3H), 3.77-3.50 (m, 3H),3.52-3.36 (m, 3H), 2.27-1.91 (m, 2H) 85 N-(4-{[(3R)-1- ¹H NMR (300 MHz,DMSO-d₆) δ 8.76 (bs, (ESI(+)) (cyclopropylcarbonyl)pyrrolidin- 1H),8.69-8.62 (m, 1H), 8.41 (s, 1H), m/e 407 3- 8.26 (dd, J = 5.0, 3.0 Hz,1H), 7.73 (ddd, J = 7.6, (M + H)⁺ yl]oxy}phenyl)-3- 5.2, 2.2 Hz, 1H),7.41 (dd, J = 9.0, 2.0 Hz, (pyridin-3- 2H), 6.87 (dd, J = 9.0, 7.5 Hz,2H), 4.98 (d, yl)azetidine-1- J = 32.2 Hz, 2H), 4.49-4.23 (m, 2H),carboxamide 4.08-3.88 (m, 3H), 3.91-3.64 (m, 2H), 3.34 (dd, J = 19.2,9.5 Hz, 1H), 2.31-1.91 (m, 2H), 1.74 (ddd, J = 12.8, 10.5, 6.5 Hz, 1H),0.84-0.36 (m, 4H) 86 N-[4-({(3R)-1-[(2S)- ¹H NMR (300 MHz, DMSO-d₆) δ(ESI(+)) 2- 8.80-8.64 (m, 2H), 8.68 (d, J = 4.3 Hz, 1H), m/e 423methylbutanoyl]pyrrolidin- 8.41 (s, 1H), 8.34-8.25 (m, 1H), 7.77 (ddd, J= 7.9, (M + H)⁺ 3- 5.3, 2.5 Hz, 1H), 7.45-7.37 (m, 2H),yl}oxy)phenyl]-3- 6.91-6.79 (m, 2H), 4.95 (d, J = 23.5 Hz, (pyridin-3-1H), 4.43-4.27 (m, 2H), 3.99 (dd, J = 6.5, yl)azetidine-1- 4.7 Hz, 3H),3.82-3.30 (m, 2H), carboxamide 2.20-1.96 (m, 2H), 1.61-1.42 (m, 1H),1.28 (tt, J = 14.1, 7.1 Hz, 1H), 1.00 (d, J = 6.7 Hz, 2H), 0.93 (d, J =6.7 Hz, 2H), 0.82 (td, J = 7.4, 2.2 Hz, 4H) 87 N-(4-{[(3R)-1- ¹H NMR(300 MHz, DMSO-d₆) δ 8.76 (bs, (ESI(+)) butanoylpyrrolidin-3- 1H), 8.66(dd, J = 5.2, 1.4 Hz, 1H), 8.41 (s, m/e 409 yl]oxy}phenyl)-3- 1H),8.30-8.22 (m, 1H), 7.78-7.69 (m, (M + H)⁺ (pyridin-3- 1H), 7.42 (d, J =1.0 Hz, 2H), yl)azetidine-1- 6.90-6.80 (m, 2H), 4.95 (d, J = 22.7 Hz,1H), carboxamide 4.45-4.24 (m, 2H), 4.08-3.90 (m, 3H), 3.63-3.44 (m,3H), 2.29-1.97 (m, 3H), 1.60-1.42 (m, 3H), 0.93-0.83 (m, 4H) 883-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆) δ 8.76 (s, (ESI(+))(4-{[(3S)-1- 1H), 8.66 (d, J = 4.5 Hz, 1H), 8.41 (s, 1H), m/e 465(tetrahydro-2H- 8.27 (d, J = 7.9 Hz, 1H), 7.83-7.57 (m, (M + H)⁺pyran-4- 1H), 7.45-7.37 (m, 2H), 6.89-6.80 (m, ylacetyl)pyrrolidin-3-2H), 4.95 (d, J = 22.0 Hz, 2H), yl]oxy}phenyl)azetidine- 4.80-4.39 (m,4H), 4.38 (q, J = 5.7 Hz, 3H), 1-carboxamide 4.10-3.87 (m, 2H),3.71-3.44 (m, 2H), 3.38-3.15 (m, 2H), 2.21 (d, J = 6.8 Hz, 2H),2.18-1.84 (m, 2H), 1.64-1.51 (m, 2H), 1.30-0.95 (m, 2H) 89N-(4-{[(3S)-1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.78 (bs, (ESI(+))methylpropanoyl)pyrrolidin- 1H), 8.68 (d, J = 4.9 Hz, 1H), 8.41 (s, 1H),m/e 409 3- 8.35-8.27 (m, 1H), 7.82-7.73 (m, 1H), (M + H)⁺yl]oxy}phenyl)-3- 7.49-7.26 (m, 2H), 6.91-6.80 (m, 2H), (pyridin-3- 4.95(d, J = 25.5 Hz, 1H), 4.43-4.32 (m, yl)azetidine-1- 2H), 4.06-3.90 (m,3H), 3.63-3.47 (m, carboxamide 3H), 2.81-2.54 (m, 1H), 2.29-1.94 (m,3H), 1.09-0.89 (m, 6H) 90 3-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆)δ 8.79 (bs, (ESI(+)) [4-({(3S)-1-[(2S)- 1H), 8.68 (d, J = 5.3 Hz, 1H),8.41 (s, 1H), m/e 437 tetrahydrofuran-2- 8.35-8.27 (m, 1H), 7.82-7.73(m, 1H), (M + H)⁺ ylcarbonyl]pyrrolidin- 7.45-7.38 (m, 2H), 6.91-6.78(m, 2H), 3- 4.96 (d, J = 23.1 Hz, 1H), 4.58-4.31 (m,yl}oxy)phenyl]azetidine- 3H), 4.08-3.92 (m, 3H), 3.86-3.44 (m,1-carboxamide 6H), 2.28-1.70 (m, 6H) 91 3-(pyridin-3-yl)-N- (ESI(+))[4-({(3S)-1-[(2R)- m/e 437 tetrahydrofuran-2- (M + H)⁺ylcarbonyl]pyrrolidin- 3- yl}oxy)phenyl]azetidine- 1-carboxamide 923-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆) δ 8.81 (bs, (ESI(+))(4-{[(3S)-1- 1H), 8.70 (d, J = 5.4 Hz, 1H), 8.42 (s, 1H), m/e 437(tetrahydrofuran-3- 8.36 (dd, J = 9.0, 2.5 Hz, 1H), (M + H)⁺ylcarbonyl)pyrrolidin- 7.86-7.77 (m, 1H), 7.45-7.38 (m, 2H), 3-6.94-6.72 (m, 2H), 5.75 (s, 1H), 5.03-4.89 (m, 1H),yl]oxy}phenyl)azetidine- 4.40-4.33 (m, 2H), 4.07-3.73 (m, 6H),1-carboxamide 3.55-3.49 (m, 2H), 3.43-3.09 (m, 2H), 2.29-1.86 (m, 5H) 93N-(4-{[(3S)-1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.80 (bs, (ESI(+))(cyclopropylacetyl)pyrrolidin- 1H), 8.69 (d, J = 5.3 Hz, 1H), 8.41 (s,1H), m/e 421 3- 8.38-8.29 (m, 1H), 7.79 (ddd, J = 7.9, 5.4, (M + H)⁺yl]oxy}phenyl)-3- 2.3 Hz, 1H), 7.44-7.37 (m, 2H), (pyridin-3- 6.91-6.76(m, 2H), 6.71-5.35 (m, 2H), yl)azetidine-1- 5.01-4.88 (m, 1H), 4.40-4.33(m, 2H), carboxamide 4.06-3.93 (m, 3H), 3.76-3.26 (m, 2H), 2.30-1.90 (m,4H), 1.04-0.86 (m, 1H), 0.49-0.35 (m, 2H), 0.17-0.07 (m, 2H) 94N-(4-{[(3S)-1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.78 (d, J = 2.1 Hz,(ESI(+)) hydroxy-2- 1H), 8.67 (dd, J = 5.2, 1.4 Hz, m/e 425methylpropanoyl)pyrrolidin- 1H), 8.41 (s, 1H), 8.34-8.26 (m, 1H), (M +H)⁺ 3- 7.81-7.73 (m, 1H), 7.31 (dd, J = 56.7, 9.0 Hz, yl]oxy}phenyl)-3-2H), 6.89-6.81 (m, 2H), 4.92 (d, J = 25.9 Hz, (pyridin-3- 1H), 4.43-4.31(m, 2H), yl)azetidine-1- 4.13-3.92 (m, 4H), 3.87-3.56 (m, 2H), 3.44 (dd,J = 22.1, carboxamide 12.9 Hz, 2H), 2.15-1.90 (m, 2H), 1.34-1.23 (m,4H), 1.20 (s, 1H) 95 N-(4-{[(3S)-1- ¹H NMR (300 MHz, DMSO-d₆) δ (ESI(+))benzoylpyrrolidin-3- 8.80-8.74 (m, 1H), 8.70-8.63 (m, 1H), m/e 443yl]oxy}phenyl)-3- 8.45-8.36 (m, 1H), 8.33-8.24 (m, 1H), (M + H)⁺(pyridin-3- 7.81-7.71 (m, 1H), 7.58-7.30 (m, 7H), 6.90 (d,yl)azetidine-1- J = 8.6 Hz, 1H), 6.81 (d, J = 8.6 Hz, 1H), carboxamide4.96 (d, J = 25.8 Hz, 2H), 4.40-4.33 (m, 2H), 3.98 (d, J = 2.8 Hz, 2H),3.86-3.75 (m, 1H), 3.71-3.34 (m, 3H), 2.27-1.99 (m, 2H) 963-(pyridin-3-yl)-N- ¹H NMR (300 MHz, DMSO-d₆) δ 8.76 (bs, (ESI(+))(4-{[(3S)-1-(3,3,3- 1H), 8.66 (d, J = 5.1 Hz, 1H), 8.41 (s, 1H), m/e 449trifluoropropanoyl)pyrrolidin- 8.30-8.22 (m, 1H), 7.78-7.69 (m, 1H),(M + H)⁺ 3- 7.45-7.38 (m, 2H), 6.91-6.81 (m, 2H),yl]oxy}phenyl)azetidine- 4.97 (d, J = 20.8 Hz, 2H), 4.40-4.32 (m,1-carboxamide 2H), 4.04-3.91 (m, 3H), 3.83-3.20 (m, 5H), 2.29-1.97 (m,2H) 97 N-(4-{[(3S)-1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.78 (s, (ESI(+))(cyclopropylcarbonyl)pyrrolidin- 1H), 8.68 (d, J = 5.3 Hz, 1H), 8.41 (s,1H), m/e 407 3- 8.34-8.26 (m, 1H), 7.81-7.72 (m, 1H), (M + H)⁺yl]oxy}phenyl)-3- 7.45-7.37 (m, 2H), 6.92-6.81 (m, 2H), (pyridin-3-6.67-4.84 (m, 4H), 4.43-4.31 (m, 2H), yl)azetidine-1- 3.91-3.63 (m, 2H),3.58-3.46 (m, 2H), carboxamide 2.29-1.96 (m, 2H), 1.93-1.66 (m, 1H),0.80-0.64 (m, 4H) 98 N-[4-({(3S)-1-[(2S)- ¹H NMR (300 MHz, DMSO-d₆) δ8.78 (bs, (ESI(+)) 2- 1H), 8.68 (d, J = 5.3 Hz, 1H), 8.41 (s, 1H), m/e423 methylbutanoyl]pyrrolidin- 8.35-8.27 (m, 1H), 7.82-7.73 (m, 2H),(M + H)⁺ 3- 7.40 (t, J = 6.2 Hz, 2H), 6.90-6.80 (m, yl}oxy)phenyl]-3-2H), 4.95 (d, J = 24.2 Hz, 2H), (pyridin-3- 4.43-4.32 (m, 2H), 4.01 (dd,J = 12.9, 5.8 Hz, 3H), yl)azetidine-1- 3.80-3.46 (m, 3H), 2.28-1.95 (m,2H), carboxamide 1.65-1.40 (m, 1H), 1.39-1.17 (m, 1H), 0.98 (dd, J =6.7, 3.2 Hz, 3H), 0.83 (t, J = 7.4 Hz, 2H), 0.75 (d, J = 7.4 Hz, 1H) 99N-(4-{[(3S)-1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.80 (bs, (ESI(+))butanoylpyrrolidin-3- 1H), 8.69 (d, J = 5.3 Hz, 1H), 8.42 (s, 1H), m/e409 yl]oxy}phenyl)-3- 8.38-8.30 (m, 1H), 7.94-7.75 (m, 1H), (M + H)⁺(pyridin-3- 7.42 (ddd, J = 9.6, 7.6, 1.8 Hz, 2H), yl)azetidine-1-7.01-6.71 (m, 2H), 5.03-4.89 (m, 2H), carboxamide 4.43-4.29 (m, 2H),4.07-3.89 (m, 3H), 3.74 (dd, J = 11.6, 4.5 Hz, 1H), 3.64-3.40 (m, 2H),3.40-3.20 (m, 1H), 2.30-2.07 (m, 2H), 2.07-1.93 (m, 1H), 1.61-1.38 (m,2H), 0.97-0.77 (m, 3H) 114 N-(4-{[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O)(ESI(+)) (cyclopropylacetyl)azetidin- ppm 8.56 (d, J = 1.83 Hz, 1 H)8.48 (dd, m/e 407 3- J = 4.58, 1.53 Hz, 1 H) 8.40 (s, 1 H) (M + H)⁺yl]oxy}phenyl)-3- 7.84-7.88 (m, 1 H) 7.39-7.43 (m, 3 H) 6.75 (d,(pyridin-3- J = 9.16 Hz, 2 H) 4.92-4.97 (m, 1 H) yl)azetidine-1- 4.51(dd, J = 9.00, 6.87 Hz, 1 H) 4.36 (t, J = 8.24 Hz, carboxamide 2 H) 4.26(dd, J = 10.53, 6.56 Hz, 1 H) 4.03 (dd, J = 9.46, 3.36 Hz, 1 H)3.92-3.96 (m, 2 H) 3.83-3.91 (m, 1 H) 3.74 (dd, J = 10.53, 3.51 Hz, 1 H)2.02 (d, J = 6.71 Hz, 2 H) 0.88-0.97 (m, 1 H) 0.41-0.46 (m, 2 H)0.08-0.12 (m, 2 H) 115 N-(4-{[1-(furan-2- ¹H NMR (400 MHz, DMSO-d₆/D₂O)(ESI(+)) ylcarbonyl)azetidin- ppm 8.58 (s, 1 H) 8.50 (d, J = 4.27 Hz, 1H) m/e 419 3-yl]oxy}phenyl)-3- 8.41 (s, 1 H) 7.84-7.91 (m, 2 H) (M + H)⁺(pyridin-3- 7.42-7.46 (m, 3 H) 7.07-7.08 (m, 1 H) yl)azetidine-1-6.76-6.81 (m, 2 H) 6.64 (dd, J = 3.66, 1.83 Hz, 1 carboxamide H)4.44-4.51 (m, 1 H) 4.36 (t, J = 8.24 Hz, 3 H) 3.93-3.97 (m, 2 H)3.84-3.92 (m, 2 H) 117 N-{4-[(1- ¹H NMR (400 MHz, DMSO-d₆/D₂O (ESI(+))pentanoylazetidin-3- Temp = 90° C.) δ ppm 8.59-8.39 (m, 2H), m/e 409yl)oxy]phenyl}-3- 7.88-7.67 (m, 1H), 7.48-7.23 (m, 3H), (M + H)⁺(pyridin-3- 6.89-6.63 (m, 2H), 5.15-4.84 (m, 1H), yl)azetidine-1-4.51-4.26 (m, 3H), 4.07-3.84 (m, 4H), carboxamide 2.21-2.00 (m, 2H),1.61-1.41 (m, 2H), 1.41-1.16 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H) 118N-[4-({1-[(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))methoxyethoxy)acetyl]azetidin- Temp = 90° C.) δ ppm 8.61-8.40 (m, 2H),m/e 441 3- 7.90-7.73 (m, 1H), 7.51-7.31 (m, 3H), (M + H)⁺yl}oxy)phenyl]-3- 6.89-6.66 (m, 2H), 5.09-4.88 (m, 1H), (pyridin-3- 4.39(t, J = 8.3 Hz, 4H), 4.08-3.83 (m, yl)azetidine-1- 7H), 3.57 (dd, J =5.8, 3.7 Hz, 2H), carboxamide 3.52-3.40 (m, 2H) 119 N-(4-{[1- ¹H NMR(400 MHz, DMSO-d₆/D₂O, (ESI(+)) (ethoxyacetyl)azetidin- Temp = 90° C.) δppm 8.66-8.29 (m, 2H), m/e 411 3-yl]oxy}phenyl)- 7.81 (dt, J = 7.9, 2.0Hz, 1H), (M + H)⁺ 3-(pyridin-3- 7.57-7.35 (m, 3H), 6.84-6.65 (m, 2H),yl)azetidine-1- 5.19-4.85 (m, 1H), 4.39 (t, J = 8.4 Hz, 4H), carboxamide4.06-3.82 (m, 7H), 3.49 (q, J = 7.0 Hz, 2H), 1.13 (t, J = 7.0 Hz, 3H)120 N-(4-{[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(methoxyacetyl)azetidin- Temp = 90° C.) δ ppm 8.65-8.38 (m, 2H), m/e 3973- 7.91-7.72 (m, 1H), 7.49-7.32 (m, 3H), (M + H)⁺ yl]oxy}phenyl)-3-6.81-6.65 (m, 2H), 5.11-4.92 (m, 1H), (pyridin-3- 4.46-4.33 (m, 3H),4.06-3.85 (m, 6H), yl)azetidine-1- 3.30 (s, 3H) carboxamide 121N-(4-{[1-(3- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))methylpentanoyl)azetidin- Temp = 90° C.) δ ppm 8.61-8.52 (m, 1H), m/e423 3- 8.52-8.41 (m, 1H), 7.88-7.72 (m, 1H), (M + H)⁺ yl]oxy}phenyl)-3-7.49-7.24 (m, 3H), 6.87-6.69 (m, 2H), (pyridin-3- 5.09-4.84 (m, 1H),4.51-4.28 (m, 4H), yl)azetidine-1- 4.07-3.83 (m, 5H), 2.18-2.02 (m, 1H),carboxamide 1.93 (t, J = 6.6 Hz, 1H), 1.84-1.67 (m, 1H), 1.43-1.28 (m,1H), 1.28-1.12 (m, 1H), 1.00-0.74 (m, 7H) 122 N-[4-({1-[(1S,4R)- ¹H NMR(400 MHz, DMSO-d₆/D₂O, (ESI(+)) bicyclo[2.2.1]hept-2- Temp = 90° C.) δppm 8.54 (d, J = 2.1 Hz, m/e 461 ylacetyl]azetidin-3- 1H), 8.46 (dd, J =4.8, 1.4 Hz, 1H), 7.81 (dt, (M + H)⁺ yl}oxy)phenyl]-3- J = 7.9, 1.9 Hz,1H), 7.44-7.31 (m, 3H), (pyridin-3- 6.85-6.71 (m, 3H), 5.03-4.87 (m,1H), yl)azetidine-1- 4.39 (t, J = 8.3 Hz, 4H), 4.02-3.85 (m, carboxamide5H), 2.33-2.06 (m, 3H), 1.87-1.63 (m, 2H), 1.34-1.24 (m, 2H), 1.20-1.07(m, 4H), 1.04 (t, J = 10.8 Hz, 4H) 123 N-(4-{[1-(2,3- ¹H NMR (400 MHz,DMSO-d₆/D₂O, (ESI(+)) dimethylbutanoyl)azetidin- Temp = 90° C.) δ ppm8.54 (t, J = 3.5 Hz, 1H), m/e 423 3- 8.48-8.41 (m, 1H), 7.95-7.69 (m,1H), (M + H)⁺ yl]oxy}phenyl)-3- 7.50-7.31 (m, 3H), 6.81-6.69 (m, 2H),(pyridin-3- 5.04-4.87 (m, 1H), 4.46-4.24 (m, 4H), yl)azetidine-1-4.06-3.81 (m, 5H), 2.22-2.08 (m, 1H), carboxamide 1.78-1.57 (m, 1H),0.97 (d, J = 6.8 Hz, 3H), 0.93-0.82 (m, 6H) 124 N-(4-{[1-(4- ¹H NMR (400MHz, DMSO-d₆/D₂O, (ESI(+)) methylpentanoyl)azetidin- Temp = 90° C.) δppm 8.55 (t, J = 3.7 Hz, 1H), m/e 423 3- 8.49-8.40 (m, 1H), 7.92-7.72(m, 1H), (M + H)⁺ yl]oxy}phenyl)-3- 7.55-7.32 (m, 3H), 6.86-6.54 (m,2H), (pyridin-3- 5.06-4.85 (m, 1H), 4.50-4.25 (m, 4H), yl)azetidine-1-4.02-3.82 (m, 5H), 2.07 (dd, J = 13.9, 6.0 Hz, carboxamide 2H),1.64-1.48 (m, 1H), 1.40 (dd, J = 15.2, 6.9 Hz, 2H), 0.87 (d, J = 6.5 Hz,6H) 125 N-[4-({1-[(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))methylcyclopropyl)carbonyl]azetidin- Temp = 90° C.) δ ppm 8.54 (t, J =3.8 Hz, 1H), m/e 407 3- 8.52-8.43 (m, 1H), 7.89-7.74 (m, 1H), (M + H)⁺yl}oxy)phenyl]-3- 7.47-7.32 (m, 3H), 6.92-6.69 (m, 2H), (pyridin-3-5.10-4.89 (m, 1H), 4.48-4.33 (m, 4H), yl)azetidine-1- 4.05-3.82 (m, 5H),1.34-1.11 (m, 2H), carboxamide 1.09-1.05 (m, 3H), 1.03-0.89 (m, 1H),0.70-0.46 (m, 1H) 126 3-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O,(ESI(+)) (4-{[1-(4,4,4- Temp = 90° C.) δ ppm 8.55 (t, J = 3.6 Hz, 1H),m/e 449 trifluorobutanoyl)azetidin- 8.52-8.39 (m, 1H), 7.89-7.74 (m,1H), (M + H)⁺ 3- 7.43-7.28 (m, 3H), 6.83-6.69 (m, 2H),yl]oxy}phenyl)azetidine- 5.10-4.88 (m, 1H), 4.48-4.30 (m, 3H),1-carboxamide 4.06-3.78 (m, 5H), 2.51-2.44 (m, 2H), 2.36 (dd, J = 13.3,5.7 Hz, 2H) 127 N-(4-{[1-(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))methylpropanoyl)azetidin- Temp = 90° C.) δ ppm 8.54 (d, J = 2.1 Hz, m/e395 3- 1H), 8.51-8.38 (m, 1H), 7.88-7.76 (m, (M + H)⁺ yl]oxy}phenyl)-3-1H), 7.51-7.31 (m, 3H), 6.79-6.65 (m, (pyridin-3- 2H), 5.04-4.88 (m,1H), 4.39 (t, J = 8.4 Hz, yl)azetidine-1- 4H), 3.97 (dd, J = 8.0, 6.0Hz, 3H), carboxamide 3.93-3.77 (m, 2H), 2.48 (d, J = 6.8 Hz, 1H), 1.00(d, J = 6.8 Hz, 6H) 128 N-(4-{[1-(2,2- ¹H NMR (400 MHz, DMSO-d₆/D₂O,(ESI(+)) dimethylpropanoyl)azetidin- Temp = 90° C.) δ ppm 8.55 (dd, J =6.6, 1.8 Hz, m/e 409 3- 1H), 8.52-8.43 (m, 1H), (M + H)⁺yl]oxy}phenyl)-3- 7.88-7.74 (m, 1H), 7.47-7.27 (m, 3H), (pyridin-3-6.85-6.60 (m, 2H), 5.05-4.91 (m, 1H), yl)azetidine-1- 4.66-4.46 (m, 2H),4.39 (dd, J = 10.5, 6.3 Hz, 2H), carboxamide 4.11-3.94 (m, 4H),3.93-3.80 (m, 1H), 1.13 (s, 9H) 129 N-{4-[(1- ¹H NMR (400 MHz,DMSO-d₆/D₂O, (ESI(+)) butanoylazetidin-3- Temp = 90° C.) δ ppm 8.54 (d,J = 2.1 Hz, m/e 395 yl)oxy]phenyl}-3- 1H), 8.46 (dd, J = 4.8, 1.5 Hz,1H), 7.81 (dt, (M + H)⁺ (pyridin-3- J = 7.8, 1.9 Hz, 1H), 7.46-7.35 (m,3H), yl)azetidine-1- 6.85-6.67 (m, 2H), 5.02-4.89 (m, 1H), carboxamide4.39 (t, J = 8.4 Hz, 4H), 4.01-3.84 (m, 4H), 2.06 (t, J = 7.3 Hz, 2H),1.52 (h, J = 7.3 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H) 130 N-{4-[(1- ¹H NMR(400 MHz, DMSO-d₆/D₂O, (ESI(+)) propanoylazetidin-3- Temp = 90° C.) δppm 8.54 (t, J = 3.3 Hz, 1H), m/e 381 yl)oxy]phenyl}-3- 8.51-8.41 (m,1H), 7.93-7.70 (m, 1H), (M + H)⁺ (pyridin-3- 7.50-7.31 (m, 3H),6.84-6.72 (m, 2H), yl)azetidine-1- 5.00-4.88 (m, 1H), 4.49-4.32 (m, 4H),carboxamide 4.08-3.82 (m, 5H), 2.19-2.02 (m, 2H), 1.00 (t, J = 7.5 Hz,3H) 131 N-(4-{[1-(2,2- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))dimethylbutanoyl)azetidin- Temp = 90° C.) δ ppm 8.54 (t, J = 2.6 Hz,1H), m/e 423 3- 8.51-8.38 (m, 1H), 7.92-7.73 (m, 1H), (M + H)⁺yl]oxy}phenyl)-3- 7.46-7.34 (m, 3H), 6.86-6.67 (m, 2H), (pyridin-3-5.02-4.88 (m, 1H), 4.64-4.46 (m, 2H), yl)azetidine-1- 4.39 (t, J = 8.4Hz, 2H), 4.07-3.96 (m, carboxamide 4H), 3.92-3.84 (m, 1H), 1.49 (q, J =7.4 Hz, 2H), 1.09 (s, 6H), 0.80 (t, J = 7.4 Hz, 3H) 132 N-(4-{[1-(3- ¹HNMR (400 MHz, DMSO-d₆/D₂O, (ESI(+)) methylbutanoyl)azetidin- Temp = 90°C.) δ ppm 8.54 (d, J = 2.1 Hz, m/e 409 3- 1H), 8.46 (dd, J = 4.7, 1.4Hz, 1H), (M + H)⁺ yl]oxy}phenyl)-3- 7.89-7.73 (m, 1H), 7.48-7.30 (m,3H), (pyridin-3- 6.87-6.74 (m, 2H), 5.00-4.89 (m, 1H), 4.39 (t, J = 8.4Hz, yl)azetidine-1- 4H), 4.08-3.79 (m, 5H), carboxamide 1.99-1.86 (m,3H), 1.02-0.85 (m, 6H) 133 N-(4-{[1-(3,3- ¹H NMR (400 MHz, DMSO-d₆/D₂O,(ESI(+)) dimethylbutanoyl)azetidin- Temp = 90° C.) δ ppm 8.54 (d, J =2.0 Hz, m/e 423 3- 1H), 8.46 (dd, J = 4.8, 1.4 Hz, 1H), (M + H)⁺yl]oxy}phenyl)-3- 7.94-7.74 (m, 1H), 7.47-7.26 (m, 3H), 6.76 (d,(pyridin-3- J = 9.0 Hz, 2H), 5.04-4.83 (m, 1H), yl)azetidine-1- 4.39 (t,J = 8.3 Hz, 3H), 3.96 (dd, J = 16.5, 8.5 Hz, carboxamide 3H), 3.88 (dd,J = 14.3, 6.0 Hz, 2H), 1.98 (s, 2H), 0.99 (s, 9H) 1343-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(4-{[1-(3,3,3- Temp = 90° C.) δ ppm 8.54 (d, J = 2.1 Hz, m/e 435trifluoropropanoyl)azetidin- 1H), 8.51-8.38 (m, 1H), 7.97-7.74 (m, (M +H)⁺ 3- 1H), 7.52-7.27 (m, 3H), 6.87-6.68 (m, yl]oxy}phenyl)azetidine-2H), 5.12-4.93 (m, 1H), 4.58 (s, 1H), 1-carboxamide 4.44-4.31 (m, 3H),4.14 (s, 1H), 4.03-3.80 (m, 4H), 3.33-3.26 (m, 2H) 135 N-[4-({1-[(1- ¹HNMR (400 MHz, DMSO-d₆/D₂O, (ESI(+)) methylcyclopropyl)carbonyl]azetidin-Temp = 90° C.) δ ppm 8.62-8.52 (m, 1H), m/e 407 3- 8.52-8.36 (m, 1H),7.90-7.72 (m, 1H), (M + H)⁺ yl}oxy)phenyl]-3- 7.46-7.33 (m, 3H),6.83-6.70 (m, 2H), (pyridin-3- 5.06-4.84 (m, 1H), 4.59-4.46 (m, 2H),yl)azetidine-1- 4.46-4.29 (m, 2H), 4.05-3.95 (m, 4H), carboxamide3.91-3.80 (m, 1H), 1.25 (s, 3H), 1.09-0.81 (m, 2H), 0.63-0.39 (m, 2H)136 N-(4-{[1-(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))methylpentanoyl)azetidin- Temp = 90° C.) δ ppm 8.54 (s, 1H), 8.46 (d, J= 4.7 Hz, m/e 423 3- 1H), 7.81 (d, J = 7.9 Hz, 1H), (M + H)⁺yl]oxy}phenyl)-3- 7.40 (t, J = 7.5 Hz, 3H), 6.76 (d, J = 8.8 Hz,(pyridin-3- 2H), 4.97 (s, 1H), 4.39 (t, J = 8.2 Hz, 4H), yl)azetidine-1-4.12-3.78 (m, 5H), 2.37 (dd, J = 12.8, 6.3 Hz, carboxamide 1H),1.63-1.41 (m, 1H), 1.26 (s, 4H), 0.99 (d, J = 6.7 Hz, 3H), 0.86 (t, J =6.9 Hz, 3H) 137 N-{4-[(1- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))acetylazetidin-3- Temp = 90° C.) δ ppm 8.54 (d, J = 2.1 Hz, m/e 367yl)oxy]phenyl}-3- 1H), 8.46 (dd, J = 4.8, 1.5 Hz, 1H), (M + H)⁺(pyridin-3- 7.85-7.77 (m, 1H), 7.46-7.33 (m, 3H), yl)azetidine-1-6.81-6.69 (m, 2H), 5.05-4.84 (m, 1H), 4.39 (t, J = 8.4 Hz, carboxamide4H), 4.03-3.93 (m, 3H), 3.93-3.83 (m, 1H), 1.80 (s, 3H) 138 N-(4-{[1- ¹HNMR (400 MHz, DMSO-d₆/D₂O, (ESI(+)) (cyclohexylacetyl)azetidin- Temp =90° C.) δ ppm 8.54 (d, J = 2.1 Hz, m/e 449 3- 1H), 8.52-8.36 (m, 1H),7.85-7.73 (m, (M + H)⁺ yl]oxy}phenyl)-3- 1H), 7.43-7.26 (m, 3H),6.77-6.70 (m, (pyridin-3- 2H), 5.13-4.90 (m, 1H), 4.41 (dd, J = 24.5,yl)azetidine-1- 16.0 Hz, 4H), 4.04-3.77 (m, 5H), 1.96 (t, J = 6.8 Hz,carboxamide 2H), 1.72-1.66 (m, 4H), 1.28-1.13 (m, 4H), 1.03-0.91 (m, 3H)139 N-(4-{[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(cyclohexylcarbonyl)azetidin- Temp = 90° C.) δ ppm 8.54 (d, J = 2.2 Hz,m/e 435 3- 1H), 8.51-8.42 (m, 1H), 7.88-7.74 (m, (M + H)⁺yl]oxy}phenyl)-3- 1H), 7.50-7.28 (m, 3H), 6.83-6.66 (m, (pyridin-3- 2H),5.04-4.87 (m, 1H), 4.39 (t, J = 8.4 Hz, yl)azetidine-1- 4H), 4.04-3.82(m, 5H), carboxamide 2.31-2.15 (m, 1H), 1.76-1.57 (m, 6H), 1.38-1.24 (m,4H) 140 N-(4-{[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(cyclopropylcarbonyl)azetidin- Temp = 90° C.) δ ppm 8.54 (d, J = 2.1 Hz,m/e 393 3- 1H), 8.49-8.30 (m, 1H), 7.91-7.72 (m, (M + H)⁺yl]oxy}phenyl)-3- 1H), 7.48-7.34 (m, 3H), 6.85-6.68 (m, (pyridin-3- 2H),5.12-4.93 (m, 1H), 4.55-4.34 (m, yl)azetidine-1- 4H), 4.08-3.84 (m, 5H),1.63-1.47 (m, carboxamide 1H), 0.82-0.66 (m, 5H) 141 3-(pyridin-3-yl)-N-¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+)) (4-{[1-(thiophen-2- Temp = 90°C.) δ ppm 8.55 (d, J = 1.9 Hz, m/e 435 ylcarbonyl)azetidin- 1H), 8.47(dd, J = 4.8, 1.3 Hz, 1H), 7.82 (d, (M + H)⁺ 3- J = 7.9 Hz, 1H), 7.75(dd, J = 5.0, 1.0 Hz, yl]oxy}phenyl)azetidine- 1H), 7.53 (dd, J = 3.7,1.0 Hz, 1H), 1-carboxamide 7.49-7.35 (m, 3H), 7.16 (dd, J = 4.9, 3.8 Hz,1H), 6.86-6.70 (m, 2H), 5.18-4.96 (m, 1H), 4.68 (s, 2H), 4.40 (t, J =8.4 Hz, 2H), 4.19 (s, 1H), 4.03-3.83 (m, 4H) 142 N-(4-{[1- ¹H NMR (400MHz, DMSO-d₆/D₂O, (ESI(+)) (cyclopentylcarbonyl)azetidin- Temp = 90° C.)δ ppm 8.54 (d, J = 2.1 Hz, m/e 421 3- 1H), 8.46 (dd, J = 4.8, 1.5 Hz,1H), 7.81 (dt, (M + H)⁺ yl]oxy}phenyl)-3- J = 7.8, 1.9 Hz, 1H),7.47-7.31 (m, 3H), (pyridin-3- 6.83-6.70 (m, 2H), 5.05-4.90 (m, 1H),yl)azetidine-1- 4.39 (t, J = 8.4 Hz, 4H), 4.07-3.81 (m, carboxamide 5H),2.65 (dt, J = 15.1, 7.7 Hz, 1H), 1.83-1.70 (m, 2H), 1.70-1.45 (m, 6H)143 N-(4-{[1-(morpholin- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))4-ylacetyl)azetidin-3- Temp = 90° C.) δ ppm 8.68-8.50 (m, 1H), m/e 452yl]oxy}phenyl)-3- 8.52-8.39 (m, 1H), 7.94-7.73 (m, 1H), (M + H)⁺(pyridin-3- 7.46-7.33 (m, 3H), 6.86-6.63 (m, 2H), yl)azetidine-1-5.03-4.89 (m, 1H), 4.61-4.31 (m, 4H), carboxamide 4.02-3.83 (m, 5H),3.65-3.47 (m, 4H), 2.57-2.49 (m, 2H), 2.49-2.38 (m, 4H) 1443-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(4-{[1-(1,3-thiazol-5- Temp = 90° C.) δ ppm 9.19 (s, 1H), 8.55 (d, J =2.1 Hz, m/e 436 ylcarbonyl)azetidin- 1H), 8.46 (dd, J = 4.8, 1.5 Hz,(M + H)⁺ 3- 1H), 8.26 (s, 1H), 7.81 (d, J = 7.9 Hz, 1H),yl]oxy}phenyl)azetidine- 7.49-7.32 (m, 3H), 6.87-6.72 (m, 2H),1-carboxamide 5.18-4.97 (m, 1H), 4.69 (s, 2H), 4.40 (t, J = 8.4 Hz, 2H),4.21 (s, 2H), 4.03-3.94 (m, 2H), 3.89 (dt, J = 8.6, 7.2 Hz, 1H), 3.20(s, 1H) 145 N-[4-({1-[(3,5- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))dimethyl-1,2-oxazol- Temp = 90° C.) δ ppm 8.55 (t, J = 4.4 Hz, 1H), m/e436 4- 8.50-8.41 (m, 1H), 7.85-7.76 (m, 1H), (M + H)⁺yl)carbonyl]azetidin- 7.44-7.32 (m, 3H), 6.80-6.72 (m, 2H),3-yl}oxy)phenyl]-3- 5.03 (tt, J = 6.4, 4.1 Hz, 1H), (pyridin-3-4.50-4.36 (m, 4H), 4.06-3.92 (m, 4H), yl)azetidine-1- 3.92-3.82 (m, 1H),3.20 (s, 1H), 2.44 (s, 3H), 2.24 (s, carboxamide 3H) 1463-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(4-{[1-(thiophen-3- Temp = 90° C.) δ ppm 8.54 (d, J = 1.9 Hz, m/e 435ylcarbonyl)azetidin- 1H), 8.53-8.43 (m, 1H), 7.96 (dd, J = 2.9, (M + H)⁺3- 1.2 Hz, 1H), 7.81 (dd, J = 7.9, 1.8 Hz, 1H), yl]oxy}phenyl)azetidine-7.55 (dd, J = 5.1, 2.9 Hz, 1H), 1-carboxamide 7.43-7.34 (m, 4H),6.82-6.74 (m, 2H), 5.09-5.00 (m, 1H), 4.62 (s, 2H), 4.39 (t, J = 8.3 Hz,2H), 4.15 (s, 2H), 4.02-3.93 (m, 2H), 3.94-3.86 (m, 1H) 1473-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(4-{[1-(1,3-thiazol-4- Temp = 90° C.) δ ppm 9.08 (d, J = 2.0 Hz, m/e 436ylcarbonyl)azetidin- 1H), 8.54 (d, J = 2.1 Hz, 1H), 8.46 (dd, J = 4.8,(M + H)⁺ 3- 1.5 Hz, 1H), 8.28 (d, J = 2.1 Hz, 1H),yl]oxy}phenyl)azetidine- 7.91-7.73 (m, 1H), 7.50-7.30 (m, 3H),1-carboxamide 6.85-6.72 (m, 2H), 5.13-4.98 (m, 1H), 4.58 (s, 2H), 4.40(t, J = 8.4 Hz, 3H), 4.31-4.01 (m, 1H), 3.98 (dd, J = 8.0, 6.0 Hz, 2H),3.93-3.80 (m, 1H) 148 N-(4-{[1-(1,2-oxazol- ¹H NMR (400 MHz,DMSO-d₆/D₂O, (ESI(+)) 5- Temp = 90° C.) δ ppm 8.61 (t, J = 12.7 Hz, m/e420 ylcarbonyl)azetidin- 1H), 8.55 (d, J = 2.0 Hz, 1H), 8.47 (dd, J =4.7, (M + H)⁺ 3-yl]oxy}phenyl)-3- 1.3 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H),(pyridin-3- 7.47-7.38 (m, 3H), 6.96 (d, J = 1.9 Hz, yl)azetidine-1- 1H),6.86-6.72 (m, 2H), 5.16-5.06 (m, carboxamide 1H), 4.58 (s, 2H), 4.40 (t,J = 8.4 Hz, 3H), 3.97 (dt, J = 15.9, 7.8 Hz, 3H), 3.93-3.84 (m, 1H) 149N-[4-({1-[(4- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+)) methylpiperazin-1-Temp = 90° C.) δ ppm 8.59-8.51 (m, 1H), m/e 465 yl)acetyl]azetidin-3-8.51-8.38 (m, 1H), 7.85-7.78 (m, 1H), (M + H)⁺ yl}oxy)phenyl]-3-7.44-7.33 (m, 3H), 6.80-6.71 (m, 2H), (pyridin-3- 5.02-4.91 (m, 1H),4.71-4.50 (m, 1H), yl)azetidine-1- 4.46-4.32 (m, 3H), 4.06-3.95 (m, 3H),carboxamide 3.93-3.82 (m, 2H), 3.06-2.93 (m, 2H), 2.49-2.39 (m, 5H),2.38-2.28 (m, 5H), 2.16 (s, 4H) 150 N-(4-{[1-(N,N- ¹H NMR (400 MHz,DMSO-d₆/D₂O, (ESI(+)) dimethyl-beta- Temp = 90° C.) δ ppm 8.54 (s, 1H),8.46 (d, J = 4.8 Hz, m/e 424 alanyl)azetidin-3- 1H), 7.80 (d, J = 7.8Hz, 1H), (M + H)⁺ yl]oxy}phenyl)-3- 7.45-7.29 (m, 3H), 6.76 (dd, J =11.5, 4.7 Hz, (pyridin-3- 2H), 5.05-4.93 (m, 1H), 4.52 (s, 1H),yl)azetidine-1- 4.39 (t, J = 8.4 Hz, 3H), 4.11 (s, 2H), carboxamide4.05-3.94 (m, 2H), 3.90 (dd, J = 14.3, 8.1 Hz, 1H), 2.73 (s, 6H), 2.56(d, J = 6.7 Hz, 2H) 151 N-(4-{[1-(furan-3- ¹H NMR (500 MHz, DMSO-d₆,(ESI(+)) ylcarbonyl)azetidin- Temp = 90° C.) δ ppm 8.57 (d, J = 2.1 Hz,m/e 419 3-yl]oxy}phenyl)-3- 1H), 8.54-8.47 (m, 1H), 8.43 (s, 1H), (M +H)⁺ (pyridin-3- 8.19 (s, 1H), 7.92-7.84 (m, 1H), 7.76 (t, J = 1.6 Hz,yl)azetidine-1- 1H), 7.48-7.40 (m, 3H), carboxamide 6.80-6.75 (m, 2H),5.09-4.99 (m, 1H), 4.78-4.71 (m, 1H), 4.50-4.41 (m, 1H), 4.37 (t, J =8.3 Hz, 2H), 4.32 (d, J = 7.2 Hz, 1H), 3.94 (dd, J = 7.9, 6.1 Hz, 2H),3.92-3.77 (m, 2H) 152 N-[4-({1-[(1- ¹H NMR (400 MHz, DMSO-d₆/D₂O,(ESI(+)) methylcyclohexyl)carbonyl]azetidin- Temp = 90° C.) δ ppm8.60-8.53 (m, 1H), m/e 449 3- 8.52-8.42 (m, 1H), 7.81 (ddd, J = 7.9,4.7, (M + H)⁺ yl}oxy)phenyl]-3- 1.5 Hz, 1H), 7.46-7.32 (m, 3H),(pyridin-3- 6.80-6.71 (m, 3H), 4.98-4.90 (m, 1H), yl)azetidine-1-4.56-4.42 (m, 2H), 4.40 (dd, J = 10.9, 5.8 Hz, carboxamide 2H), 4.00(ddd, J = 14.0, 10.2, 8.8 Hz, 3H), 3.93-3.82 (m, 1H), 1.55-1.29 (m, 8H),1.31-1.15 (m, 4H), 1.09 (s, 4H) 153 N-(4-{[1- ¹H NMR (400 MHz,DMSO-d₆/D₂O, (ESI(+)) (cyclopentylacetyl)azetidin- Temp = 90° C.) δ ppm8.54 (d, J = 2.2 Hz, m/e 435 3- 1H), 8.46 (dd, J = 4.8, 1.5 Hz, 1H),7.81 (dt, (M + H)⁺ yl]oxy}phenyl)-3- J = 7.9, 1.9 Hz, 1H), 7.47-7.33 (m,3H), (pyridin-3- 6.83-6.72 (m, 3H), 5.04-4.85 (m, 1H), yl)azetidine-1-4.39 (t, J = 8.4 Hz, 3H), 3.99-3.93 (m, carboxamide 2H), 3.93-3.79 (m,2H), 2.14 (dt, J = 11.5, 5.8 Hz, 1H), 2.08 (d, J = 1.9 Hz, 1H),1.82-1.69 (m, 2H), 1.64-1.40 (m, 5H), 1.24-1.01 (m, 2H) 1543-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(4-{[1-(1,3-thiazol-2- Temp = 90° C.) δ ppm 8.55 (d, J = 1.9 Hz, m/e 436ylcarbonyl)azetidin- 1H), 8.52-8.40 (m, 1H), 7.99 (d, J = 3.1 Hz, (M +H)⁺ 3- 1H), 7.92 (d, J = 3.2 Hz, 1H), 7.81 (dt, yl]oxy}phenyl)azetidine-J = 7.9, 1.9 Hz, 1H), 7.48-7.38 (m, 3H), 1-carboxamide 6.85-6.77 (m,2H), 5.10 (td, J = 6.2, 3.2 Hz, 1H), 4.51 (s, 1H), 4.40 (t, J = 8.4 Hz,3H), 4.07 (s, 1H), 4.06-3.93 (m, 3H), 3.89 (dt, J = 8.5, 7.1 Hz, 1H) 1553-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O, (ESI(+))(4-{[1-(pyrrolidin-1- Temp = 90° C.) δ ppm 8.54 (s, 1H), 8.46 (d, J =4.3 Hz, m/e 436 ylacetyl)azetidin-3- 1H), 7.81 (dd, J = 7.9, 1.9 Hz,(M + H)⁺ yl]oxy}phenyl)azetidine- 1H), 7.49-7.34 (m, 3H), 6.81-6.72 (m,1-carboxamide 2H), 5.05-4.94 (m, 1H), 4.52 (s, 1H), 4.39 (t, J = 8.4 Hz,3H), 4.11 (s, 1H), 3.97 (dd, J = 8.0, 6.0 Hz, 3H), 3.94-3.88 (m, 1H),3.78 (s, 2H), 3.11 (s, 4H), 2.00-1.81 (m, 4H) 297 N-(4-{[(3R)-1-(ESI(+)) pentanoylpyrrolidin- m/e 423 3-yl]oxy}phenyl)-3- (M + H)⁺(pyridin-3- yl)azetidine-1- carboxamide 298 N-(4-{[(3R)-1-(3- (ESI(+))methylpentanoyl)pyrrolidin- m/e 437 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 299 N-(4-{[1- (ESI(+))(bicyclo[2.2.1]hept-2- m/e 475 ylacetyl)pyrrolidin-3- (M + H)⁺yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 300N-(4-{[(3R)-1- (ESI(+)) (cyclopentylacetyl)pyrrolidin- m/e 449 3- (M +H)⁺ yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 301N-[4-({(3R)-1-[(2- (ESI(+)) methylcyclopropyl)carbonyl]pyrrolidin- m/e421 3- (M + H)⁺ yl}oxy)phenyl]-3- (pyridin-3- yl)azetidine-1-carboxamide 302 N-(4-{[(3R)-1- (ESI(+)) (morpholin-4- m/e 466ylacetyl)pyrrolidin-3- (M + H)⁺ yl]oxy}phenyl)-3- (pyridin-3-yl)azetidine-1- carboxamide 303 N-(4-{[(3R)-1-(furan- (ESI(+)) 3- m/e433 ylcarbonyl)pyrrolidin- (M + H)⁺ 3-yl]oxy}phenyl)-3- (pyridin-3-yl)azetidine-1- carboxamide 304 3-(pyridin-3-yl)-N- (ESI(+))(4-{[(3R)-1- m/e 450 (pyrrolidin-1- (M + H)⁺ ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine- 1-carboxamide 305 N-(4-{[(3R)-1-(5- (ESI(+))oxo-D- m/e 450 prolyl)pyrrolidin-3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 306 N-(4-{[(3R)-1-(N,N- (ESI(+))dimethyl-beta- m/e 438 alanyl)pyrrolidin-3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 307 3-(pyridin-3-yl)-N- (ESI(+))(4-{[(3R)-1-(1,3- m/e 450 thiazol-2- (M + H)⁺ ylcarbonyl)pyrrolidin- 3-yl]oxy}phenyl)azetidine- 1-carboxamide 308 3-(pyridin-3-yl)-N- (ESI(+))(4-{[(3R)-1- m/e 449 (thiophen-3- (M + H)⁺ ylcarbonyl)pyrrolidin- 3-yl]oxy}phenyl)azetidine- 1-carboxamide 309 N-[4-({(3R)-1-[(1- (ESI(+))methylcyclopropyl)carbonyl]pyrrolidin- m/e 421 3- (M + H)⁺yl}oxy)phenyl]-3- (pyridin-3- yl)azetidine-1- carboxamide 310N-[4-({(3R)-1-[(3- (ESI(+)) methylthiophen-2- m/e 463yl)carbonyl]pyrrolidin- (M + H)⁺ 3-yl}oxy)phenyl]- 3-(pyridin-3-yl)azetidine-1- carboxamide 311 3-(pyridin-3-yl)-N- (ESI(+))(4-{[(3R)-1-(4,4,4- m/e 463 trifluorobutanoyl)pyrrolidin- (M + H)⁺ 3-yl]oxy}phenyl)azetidine- 1-carboxamide 312 N-[4-({(3R)-1-[(4- (ESI(+))methylpiperazin-1- m/e 479 yl)acetyl]pyrrolidin- (M + H)⁺3-yl}oxy)phenyl]-3- (pyridin-3- yl)azetidine-1- carboxamide 313N-(4-{[(3R)-1-(5- (ESI(+)) oxo-L- m/e 450 prolyl)pyrrolidin-3- (M + H)⁺yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 314N-(4-{[(3R)-1-(3- (ESI(+)) ethoxypropanoyl)pyrrolidin- m/e 439 3- (M +H)⁺ yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 315N-(4-{[(3R)-1-(4- (ESI(+)) methylpentanoyl)pyrrolidin- m/e 437 3- (M +H)⁺ yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 316N-[4-({(3R)-1-[(1- (ESI(+)) methylcyclohexyl)carbonyl]pyrrolidin- m/e463 3- (M + H)⁺ yl}oxy)phenyl]-3- (pyridin-3- yl)azetidine-1-carboxamide 317 N-(4-{[(3R)-1- (ESI(+)) (cyclohexylacetyl)pyrrolidin-m/e 463 3- (M + H)⁺ yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1-carboxamide 318 N-(4-{[(3R)-1-(N- (ESI(+)) acetyl-L- m/e 494leucyl)pyrrolidin-3- (M + H)⁺ yl]oxy}phenyl)-3- (pyridin-3-yl)azetidine-1- carboxamide 319 N-(4-{[(3R)-1- (ESI(+))propanoylpyrrolidin- m/e 395 3-yl]oxy}phenyl)-3- (M + H)⁺ (pyridin-3-yl)azetidine-1- carboxamide 320 N-[4-({(3R)-1-[(2- (ESI(+))methoxyethoxy)acetyl]pyrrolidin- m/e 455 3- (M + H)⁺ yl}oxy)phenyl]-3-(pyridin-3- yl)azetidine-1- carboxamide 321 N-[4-({(3R)-1-[3- (ESI(+))(morpholin-4- m/e 480 yl)propanoyl]pyrrolidin- (M + H)⁺3-yl}oxy)phenyl]- 3-(pyridin-3- yl)azetidine-1- carboxamide 322N-(4-{[(3R)-1-(2,2- (ESI(+)) dimethylpropanoyl)pyrrolidin- m/e 423 3-(M + H)⁺ yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 323N-[4-({(3R)-1-[(5- (ESI(+)) methylthiophen-2- m/e 463yl)carbonyl]pyrrolidin- (M + H)⁺ 3-yl}oxy)phenyl]- 3-(pyridin-3-yl)azetidine-1- carboxamide 324 3-(pyridin-3-yl)-N- (ESI(+))(4-{[(3R)-1- m/e 449 (thiophen-2- (M + H)⁺ ylcarbonyl)pyrrolidin- 3-yl]oxy}phenyl)azetidine- 1-carboxamide 325 N-[4-({(3R)-1-[(1- (ESI(+))methyl-1H-pyrrol-2- m/e 446 yl)carbonyl]pyrrolidin- (M + H)⁺3-yl}oxy)phenyl]- 3-(pyridin-3- yl)azetidine-1- carboxamide 326N-(4-{[(3R)-1-(furan- (ESI(+)) 2- m/e 433 ylcarbonyl)pyrrolidin- (M +H)⁺ 3-yl]oxy}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 327N-[4-({(3R)-1-[3- (ESI(+)) (piperidin-1- m/e 478yl)propanoyl]pyrrolidin- (M + H)⁺ 3-yl}oxy)phenyl]- 3-(pyridin-3-yl)azetidine-1- carboxamide 328 N-(4-{[(3R)-1- (ESI(+))(ethoxyacetyl)pyrrolidin- m/e 425 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 329 N-(4-{[(3R)-1-(3,3- (ESI(+))dimethylbutanoyl)pyrrolidin- m/e 437 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 330 N-(4-{[(3R)-1-(2,2- (ESI(+))dimethylbutanoyl)pyrrolidin- m/e 437 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 331 N-(4-{[(3R)-1- (ESI(+))(methoxyacetyl)pyrrolidin- m/e 411 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 332 N-(4-{[(3R)-1- (ESI(+))(cyclohexylcarbonyl) m/e 449 pyrrolidin-3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 333 N-(4-{[(3R)-1-(3- (ESI(+))methylbutanoyl)pyrrolidin- m/e 423 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 334 N-(4-{[(3R)-1- (ESI(+))(cyclopentylcarbonyl)pyrrolidin- m/e 435 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 335 N-(4-{[(3R)-1-(2,3- (ESI(+))dimethylbutanoyl)pyrrolidin- m/e 437 3- (M + H)⁺ yl]oxy}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide

Example 9N-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamideExample 9A tert-butyl4-(4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

In a 350 mL sealed pressure flask were mixed 1-bromo-4-nitrobenzene(4.00 g, 19.80 mmol), tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate(6.74 g, 21.78 mmol), and sodium carbonate (4.41 g, 41.6 mmol) intetrahydrofuran (60 ml), water (30 ml), and methanol (10 ml). Themixture was put through three vacuum/nitrogen purge cycles.[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane (0.485 g, 0.594 mmol) was added, and the reactionmixture was heated overnight at 70° C. under nitrogen. The reactionmixture was cooled, diluted with ethyl acetate and water, and the layerswere separated. The aqueous layer was extracted with ethyl acetate andthe combined organic layers were concentrated. Normal phasechromatography provided the title compound.

Example 9B tert-butyl4-(4-aminophenyl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 1B, substitutingtert-butyl 4-(4-nitrophenyl)-5,6-dihydropyridine-1(2H)-carboxylate fortert-butyl 3-(4-nitrophenoxy)azetidine-1-carboxylate.

Example 9C tert-butyl4-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminophenyl)-5,6-dihydropyridine-1(2H)-carboxylate fortert-butyl 3-(4-aminophenoxy)azetidine-1-carboxylate.

Example 9D3-(pyridin-3-yl)-N-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1D, substitutingtert-butyl4-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenyl)piperidine-1-carboxylatefor tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate.

Example 9EN-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1E, substituting3-(pyridin-3-yl)-N-(4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)azetidine-1-carboxamideforN-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide.¹H NMR (300 MHz, DMSO-d₆) δ 8.59-8.53 (m, 2H), 8.52-8.45 (m, 1H),7.99-7.83 (m, 1H), 7.57-7.45 (m, 2H), 7.41 (ddd, J=7.8, 4.8, 0.9 Hz,1H), 7.39-7.30 (m, 2H), 6.10 (bs, 1H), 4.39 (d, J=16.4 Hz, 2H),4.23-4.14 (m, 1H), 4.13-4.06 (m, 1H), 4.07-3.82 (m, 3H), 3.72-3.65 (m,2H), 2.86-2.56 (m, 1H), 1.67-1.46 (m, 1H), 1.41-1.22 (m, 1H), 1.00 (t,J=6.8 Hz, 3H), 0.92-0.76 (m, 3H); MS (ESI(+)) m/e 419 (M+H).

TABLE 2 The following Examples were prepared essentially as described inExample 9, substituting the appropriate carboxylic acid in Example 9E.Some products were purified by flash chromatography while others werepurified by reverse-phase HPLC. Accordingly, some Examples were isolatedas trifluoroacetic acid salts. Ex Name ¹H NMR MS 10 3-(pyridine-3-yl)-N-¹H NMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.3 Hz, (ESI(+)) (4-{1-[(2R)-1H), 8.48 (dd, J = 4.7, 1.6 Hz, m/e 433 tetrahydrofuran-2- 1H), 7.87(dt, J = 7.9, 2.0 Hz, 1H), (M + H)⁺ ylcarbonyl]-1,2,3,6- 7.54-7.47 (m,2H), 7.45-7.37 (m, 1H), 7.32 (d, tetrahydropyridin-4- J = 2.1 Hz, 1H),6.09 (bs, 1H), 4.70 (ddd, J = 16.9, yl}phenyl)azetidine- 7.5, 5.6 Hz,1H), 4.38 (t, J = 8.2 Hz, 1-carboxamide 2H), 4.25-3.55 (m, 5H),2.16-1.91 (m, 2H), 1.92-1.75 (m, 2H) 11 3-(pyridine-3-yl)-N- ¹H NMR (300MHz, DMSO-d₆) δ 8.57 (d, J = 2.3 Hz, (ESI(+)) (4-{1-[(2S)- 1H), 8.48(dd, J = 4.7, 1.6 Hz, m/e 433 tetrahydrofuran-2- 1H), 7.87 (dt, J = 7.9,2.0 Hz, 1H), (M + H)⁺ ylcarbonyl]-1,2,3,6- 7.55-7.27 (m, 5H), 6.09 (bs,1H), 4.77-4.63 (m, tetrahydropyridin-4- 1H), 4.39 (t, J = 8.2 Hz, 2H),yl}phenyl)azetidine- 4.23-3.48 (m, 2H), 2.19-1.72 (m, 4H) 1-carboxamide12 N-{4-[1-(2-hydroxy- ¹H NMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.3 Hz,(ESI(+)) 2-methylpropanoyl)- 2H), 8.48 (dd, J = 4.7, 1.6 Hz, m/e 4211,2,3,6- 1H), 7.87 (dt, J = 7.9, 2.0 Hz, 1H), 7.52 (s, (M + H)⁺tetrahydropyridin-4- 1H), 7.45-7.37 (m, 1H), 7.33 (s, 1H), yl]phenyl}-3-6.14-6.08 (m, 1H), 5.43 (s, 1H), 4.38 (t, J = 8.2 Hz, (pyridin-3- 2H),4.22-3.76 (m, 6H), yl)azetidine-1- 1.40-1.23 (m, 6H) carboxamide 16N-{4-[1-(2,2- ¹H NMR (400 MHz, DMSO-d₆/D₂O (APCI(+)) dimethylbutanoyl)-Temp = 90° C.) ppm 8.47-8.61 (m, 2 H) m/e 433 1,2,3,6- 7.88 (d, 1 H)7.39-7.52 (m, J = 8.54 Hz, 3 (M + H)⁺ tetrahydropyridin-4- H) 7.27-7.38(m, J = 8.54 Hz, 2 H) 6.09 (s, yl]phenyl}-3- 1 H) 4.42 (t, J = 8.24 Hz,2 H) (pyridin-3- 4.12-4.19 (m, 2 H) 3.88-4.06 (m, 3 H) 3.74 (t, J = 5.80Hz, yl)azetidine-1- 2 H) 2.93 (d, J = 4.58 Hz, 2 H) carboxamide1.56-1.70 (m, J = 7.32 Hz, 2 H) 1.20 (s, 6 H) 0.81 (t, J = 7.32 Hz, 3 H)17 N-{4-[1-(3,3- ¹H NMR (400 MHz, DMSO-d₆/D₂O (APCI(+))dimethylbutanoyl)- Temp = 90° C.) ppm 8.61 (d, 2 H) 7.95 (d, m/e 4331,2,3,6- 1 H) 7.50-7.58 (m, J = 12.82 Hz, 1 H) (M + H)⁺tetrahydropyridin-4- 7.43-7.49 (m, J = 8.54 Hz, 2 H) 7.25-7.35 (m, 2yl]phenyl}-3- H) 6.06 (s, 1 H) 4.42 (t, J = 8.24 Hz, 2 H) (pyridin-3-4.13 (s, 2 H) 3.97-4.06 (m, 2 H) 3.69 (t, yl)azetidine-1- J = 5.65 Hz, 3H) 2.92 (s, 2 H) 2.29 (s, 2 H) carboxamide 1.01 (s, 9 H) 183-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O (APCI(+)) {4-[1-(3,3,3-Temp = 90° C.) ppm 8.61 (d, 2 H) 7.96 (d, m/e 445 trifluoropropanoyl)- 1H) 7.39-7.60 (m, 3 H) 7.26-7.36 (m, 2 (M + H)⁺ 1,2,3,6- H) 6.06 (s, 1 H)4.43 (t, J = 8.24 Hz, 2 H) tetrahydropyridin-4- 4.13 (s, 2 H) 3.89-4.05(m, 3 H) yl]phenyl}azetidine- 3.49-3.75 (m, 4 H) 2.93 (s, 2 H)1-carboxamide 19 3-(pyridin-3-yl)-N- ¹H NMR (400 MHz, DMSO-d₆/D₂O(APCI(+)) {4-[1-(4,4,4- Temp = 90° C.) ppm 8.61 (d, 2 H) 7.95 (d, m/e459 trifluorobutanoyl)- 1 H) 7.50-7.57 (m, 1 H) 7.47 (d, J = 8.54 Hz,(M + H)⁺ 1,2,3,6- 2 H) 7.32 (d, J = 8.85 Hz, 2 H) 6.06 (s, 1tetrahydropyridin-4- H) 4.42 (t, J = 8.24 Hz, 2 H) 4.13 (s, 2 H)yl]phenyl}azetidine- 3.89-4.05 (m, 3 H) 3.68 (t, J = 5.49 Hz, 31-carboxamide H) 2.93 (s, 1 H) 2.56-2.72 (m, J = 25.94 Hz, 4 H) 20N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O) (APCI(+)) (methoxyacetyl)- ppm8.64 (d, 2 H) 8.02 (d, 1 H) m/e 407 1,2,3,6- 7.55-7.61 (m, 1 H) 7.46 (d,J = 8.85 Hz, 2 H) 7.31 (d, 2 (M + H)⁺ tetrahydropyridin-4- H) 6.06 (s, 1H) 4.43 (t, J = 8.24 Hz, 2 H) yl]phenyl}-3- 4.06-4.16 (m, 4 H) 3.91-4.05(m, 3 H) (pyridin-3- 3.64 (t, J = 5.65 Hz, 2 H) 3.33 (s, 3 H)yl)azetidine-1- 2.92 (s, 2 H) carboxamide 21 N-(4-{1- ¹H NMR (400 MHz,DMSO-d₆) ppm (APCI(+)) [(methylsulfanyl)acetyl]- 8.64 (d, 2 H) 8.03 (d,J = 8.24 Hz, 1 H) m/e 423 1,2,3,6- 7.53-7.61 (m, J = 12.82 Hz, 1 H) 7.47(d, J = 8.54 Hz, (M + H)⁺ tetrahydropyridin-4- 2 H) 7.27-7.37 (m, 2 H)6.07 (s, 1 H) yl}phenyl)-3- 4.43 (t, J = 8.24 Hz, 2 H) 4.14 (s, 2 H)(pyridin-3- 3.94-4.06 (m, 3 H) 3.68 (t, J = 5.65 Hz, 2 H)yl)azetidine-1- 3.42 (s, 2 H) 2.93 (s, 2 H) 2.12 (s, 3 H) carboxamide 22N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆) ppm (APCI(+)) (ethoxyacetyl)- 8.63(d, 2 H) 8.00 (d, 1 H) 7.53-7.63 (m, m/e 421 1,2,3,6- J = 13.12 Hz, 1 H)7.46 (d, J = 8.54 Hz, 2 H) (M + H)⁺ tetrahydropyridin-4- 7.32 (d, J =8.54 Hz, 2 H) 6.06 (s, 1 H) yl]phenyl}-3- 4.43 (t, J = 8.24 Hz, 2 H)4.08-4.20 (m, 4 H) (pyridin-3- 3.92-4.07 (m, 3 H) 3.66 (t, J = 5.80 Hz,2 yl)azetidine-1- H) 3.45-3.56 (m, 2 H) 2.92 (s, 2 H) carboxamide1.10-1.20 (m, 3 H) 23 N-(4-{1-[(2- ¹H NMR (400 MHz, DMSO-d₆) ppm(APCI(+)) methoxyethoxy)acetyl]- 8.63 (d, 2 H) 8.00 (d, 1 H) 7.52-7.60(m, 1 m/e 451 1,2,3,6- H) 7.46 (d, J = 8.85 Hz, 2 H) 7.32 (d, J = 8.85Hz, (M + H)⁺ tetrahydropyridin-4- 2 H) 6.06 (s, 1 H) 4.43 (t, J = 8.24Hz, 2 yl}phenyl)-3- H) 4.19 (s, 2 H) 4.10 (s, 3 H) 3.92-4.05 (m,(pyridin-3- 3 H) 3.56-3.71 (m, 5 H) 3.47-3.53 (m, 3 yl)azetidine-1- H)2.92 (s, 2 H) carboxamide 24 N-(4-{1-[3- ¹H NMR (400 MHz, DMSO-d₆) ppm(APCI(+)) (methylsulfanyl)propanoyl]- 8.61 (d, 2 H) 7.96 (d, 1 H)7.50-7.56 (m, 1 m/e 437 1,2,3,6- H) 7.47 (d, J = 8.54 Hz, 2 H) 7.32 (d,J = 8.54 Hz, (M + H)⁺ tetrahydropyridin-4- 2 H) 6.06 (s, 1 H) 4.42 (t, J= 8.39 Hz, 2 yl}phenyl)-3- H) 4.12 (s, 2 H) 3.91-4.04 (m, 3 H) 3.67 (t,(pyridin-3- J = 5.65 Hz, 2 H) 2.92 (s, 2 H) yl)azetidine-1- 2.65-2.76(m, J = 16.33, 5.65 Hz, 4 H) 2.08 (s, 3 H) carboxamide 25 N-{4-[1- ¹HNMR (400 MHz, DMSO-d₆) ppm (APCI(+)) (cyclopropylcarbonyl)- 8.64 (d, 2H) 8.03 (d, 1 H) 7.58 (dd, J = 7.63, m/e 403 1,2,3,6- 5.49 Hz, 1 H) 7.47(d, J = 8.85 Hz, 2 H) (M + H)⁺ tetrahydropyridin-4- 7.32 (d, 2 H) 6.08(s, 1 H) 4.43 (t, J = 8.24 Hz, 2 yl]phenyl}-3- H) 4.22 (s, 2 H)3.91-4.07 (m, 3 H) 3.78 (s, (pyridin-3- 2 H) 2.93 (s, 2 H) 1.90-2.01 (m,1 H) yl)azetidine-1- 0.71-0.82 (m, 4 H) carboxamide 26 N-{4-[1- ¹H NMR(400 MHz, DMSO-d₆) ppm (APCI(+)) (cyclopropylacetyl)- 8.62 (d, 2 H) 7.96(d, 1 H) 7.50-7.55 (m, m/e 417 1,2,3,6- J = 12.21 Hz, 1 H) 7.46 (d, J =8.54 Hz, 2 H) (M + H)⁺ tetrahydropyridin-4- 7.32 (d, J = 8.54 Hz, 2 H)6.06 (s, 1 H) yl]phenyl}-3- 4.42 (t, J = 8.24 Hz, 2 H) 4.08-4.12 (m, J =2.44 Hz, (pyridin-3- 2 H) 3.90-4.04 (m, 3 H) 3.66 (t, yl)azetidine-1- J= 5.65 Hz, 2 H) 2.92 (s, 2 H) 2.32 (d, carboxamide J = 6.71 Hz, 2 H)0.95-1.06 (m, 1 H) 0.42-0.51 (m, 2 H) 0.09-0.20 (m, 2 H) 27 N-{4-[1-(2-¹H NMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.4 Hz, (ESI(+))methylpropanoyl)- 1H), 8.48 (dd, J = 4.7, 1.6 Hz, m/e 405 1,2,3,6- 1H),7.87 (dt, J = 7.9, 2.0 Hz, 1H), (M + H)⁺ tetrahydropyridin-4- 7.54-7.30(m, 5H), 6.10 (bs, 1H), 4.39 (t, J = 8.2 Hz, yl]phenyl}-3- 2H),4.23-4.15 (m, 1H), (pyridin-3- 4.11-4.04 (m, 1H), 4.01-3.86 (m, 3H),yl)azetidine-1- 3.72-3.63 (m, 2H), 3.06-2.83 (m, 1H), 2.40 (s, 1H),carboxamide 1.06-0.97 (m, 6H)

Example 13 methyl4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)benzoate

To a 20 mL vial was added 3-(azetidin-3-yl)pyridine, bistrifluoroaceticacid (75 mg, 0.207 mmol) and diisopropylethylamine (0.109 ml, 0.622mmol) in dichloromethane (2072 μl. Methyl 4-isocyanatobenzoate (47.7 mg,0.269 mmol) was added, and the mixture was stirred at room temperaturefor 2 hours and concentrated by rotary evaporation. The residue waspurified by regular phase chromatography to give the title compound. ¹HNMR (300 MHz, DMSO-d₆) δ 8.90 (s, 1H), 8.57 (d, J=2.1 Hz, 1H), 8.48 (dd,J=4.8, 1.6 Hz, 1H), 7.91-7.82 (m, 3H), 7.71-7.64 (m, 2H), 7.41 (ddd,J=7.9, 4.7, 0.8 Hz, 1H), 4.42 (t, J=8.4 Hz, 2H), 4.05-3.96 (m, 2H), 3.89(dt, J=8.1, 7.0 Hz, 1H), 3.81 (s, 1H); MS (ESI(+)) m/e 312 (M+H).

Example 14 N-(4-cyanophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 13, substituting4-isocyanatobenzonitrile for methyl 4-isocyanatobenzoate. ¹H NMR (300MHz, DMSO-d₆) δ 8.99 (s, 1H), 8.57 (d, J=2.1 Hz, 1H), 8.48 (dd, J=4.7,1.6 Hz, 1H), 7.88 (dt, J=7.9, 2.0 Hz, 1H), 7.79-7.65 (m, 4H), 7.41 (ddd,J=7.9, 4.7, 0.8 Hz, 1H), 4.42 (t, J=8.4 Hz, 2H), 4.11-3.84 (m, 3H); MS(ESI(+)) m/e 279 (M+H).

Example 15 tert-butyl4-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)butyl]piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminobutyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ8.54-8.43 (m, 1H), 7.99-7.68 (m, 1H), 7.39 (dd, J=7.9, 4.8 Hz, 1H), 6.34(t, J=5.6 Hz, 1H), 4.24-4.14 (m, 1H), 4.09-3.67 (m, 4H), 3.12-2.88 (m,2H), 2.80-2.59 (m, 2H), 1.65-1.40 (m, 3H), 1.43-1.13 (m, 7H), 1.06-0.80(m, 2H); MS (ESI(+)) m/e 417 (M+H).

Example 493-(pyridin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxamideExample 49A 4-amino-N-((tetrahydrofuran-3-yl)methyl)benzamide

The title compound was prepared as described in Example 1E, substituting(tetrahydrofuran-3-yl)methanamine forN-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamideand 4-aminobenzoic acid for (S)-2-methylbutanoic acid.

Example 49B3-(pyridin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxamide

The title compound was prepared as described in Example 1C, substituting4-amino-N-((tetrahydrofuran-3-yl)methyl)benzamide for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate. ¹H NMR (400 MHz, DMSO-d₆/D₂OTemp=90° C.) δ ppm 8.77 (d, J=1.7 Hz, 1H), 8.69-8.58 (m, 1H), 8.39 (d,J=8.1 Hz, 1H), 7.87 (dd, J=8.0, 5.4 Hz, 1H), 7.79-7.67 (m, 2H),7.67-7.30 (m, 2H), 4.62-4.36 (m, 2H), 4.16-4.02 (m, 3H), 3.78-3.68 (m,2H), 3.64 (dd, J=14.9, 7.8 Hz, 1H), 3.47 (dd, J=8.5, 5.6 Hz, 1H),3.35-3.24 (m, 2H), 2.12-1.83 (m, 1H), 1.81-1.47 (m, 1H); MS (ESI(+)) m/e381 (M+H)⁺.

Example 503-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamideExample 50A tert-butyl4-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate.

Example 50BN-(4-(piperidin-4-yl)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1D, substitutingtert-butyl4-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenyl)piperidine-1-carboxylatefor tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate.

Example 50CN-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1E, substitutingN-(4-(piperidin-4-yl)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide forN-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamideand tetrahydro-2H-pyran-4-ylacetic acid for (S)-2-methylbutanoic acid.¹H NMR (300 MHz, DMSO-d₆) δ ppm 8.58 (d, J=1.7 Hz, 1H), 8.49 (d, J=3.4Hz, 1H), 8.44 (s, 1H), 7.89 (dt, J=7.9, 1.9 Hz, 1H), 7.43 (dd, J=7.9,5.6 Hz, 3H), 7.10 (d, J=8.6 Hz, 2H), 4.55 (d, J=12.8 Hz, 1H), 4.37 (t,J=8.1 Hz, 2H), 4.04-3.76 (m, 6H), 3.08 (dd, J=17.1, 9.4 Hz, 1H),2.74-2.55 (m, 2H), 2.27 (d, J=6.9 Hz, 2H), 1.92 (ddd, J=14.8, 7.4, 3.8Hz, 1H), 1.76 (t, J=11.6 Hz, 2H), 1.65-1.08 (m, 7H); MS (ESI(+)) m/e 463(M+H).

TABLE 3 The following Examples were prepared essentially as described inExample 50, substituting the appropriate amine in Example 50A and theappropriate carboxylic acid in Example 50C. Some products were purifiedby flash chromatography while others were purified by reverse-phaseHPLC. Accordingly, some Examples were isolated as trifluoroacetic acidsalts. Ex Name ¹H NMR MS 51 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56(d, J = 2.3 Hz, (ESI(+)) hydroxy-2- 1H), 8.48 (dd, J = 4.7, 1.6 Hz, 1H),m/e 423 methylpropanoyl)piperidin- 8.45 (s, 1H), 7.86 (dt, J = 7.9, 2.0Hz, 1H), (M + H)⁺ 4- 7.46-7.37 (m, 3H), 7.10 (d, J = 8.6 Hz, 1H), 4.76(bs, yl]phenyl}-3- 1H), 4.37 (d, J = 16.2 Hz, 2H), 3.99-3.81 (m,(pyridin-3- 3H), 2.81-2.60 (m, 1H), 1.81-1.71 (m, 2H), yl)azetidine-1-1.60-1.36 (m, 2H), 1.33 (s, 6H) carboxamide 52 3-(pyridin-3-yl)- ¹H NMR(300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.3 Hz, (ESI(+)) N-(4-{1-[(2S)- 1H),8.48 (dd, J = 4.7, 1.6 Hz, 1H), m/e 435 tetrahydrofuran- 8.45 (s, 1H),7.86 (dt, J = 7.9, 1.9 Hz, 1H), (M + H)⁺ 2- 7.46-7.37 (m, 3H), 7.14-7.07(m, 2H), 4.68 (dd, J = 7.5, ylcarbonyl]piperidin- 5.7 Hz, 1H), 4.53-4.43(m, 1H), 4.37 (t, J = 8.1 Hz, 4- 2H), 4.15-4.05 (m, 1H),yl}phenyl)azetidine- 4.03-3.68 (m, 5H), 3.17-2.98 (m, 1H), 2.80-2.59 (m,1- 2H), 2.29-1.93 (m, 2H), 1.94-1.70 (m, 4H), carboxamide 1.62-1.31 (m,2H) 53 3-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.3Hz, (ESI(+)) N-{4-[1- 1H), 8.52-8.37 (m, 1H), 7.86 (dt, J = 7.9, m/e 435(tetrahydrofuran- 2.0 Hz, 1H), 7.46-7.37 (m, 3H), (M + H)⁺ 3- 7.15-7.08(m, 2H), 4.59-4.48 (m, 1H), 4.37 (t, J = 8.1 Hz, ylcarbonyl)piperidin-2H), 4.11-4.01 (m, 1H), 4- 4.00-3.80 (m, 4H), 3.78-3.62 (m, 3H),3.46-3.34 (m, yl]phenyl}azetidine- 1H), 3.20-3.02 (m, 1H), 2.77-2.59 (m,2H), 1- 2.10-1.91 (m, 2H), 1.93-1.70 (m, 2H), carboxamide 1.61-1.29 (m,2H) 54 3-(pyridin-3-yl)- ¹H NMR (400 MHz, DMSO-d₆) δ 8.56 (d, J = 2.3Hz, (ESI(+)) N-(4-{1-[(2R)- 1H), 8.48 (dd, J = 4.7, 1.6 Hz, 1H), m/e 435tetrahydrofuran- 8.45 (s, 1H), 7.86 (dt, J = 7.9, 1.9 Hz, 1H), (M + H)⁺2- 8.05-7.64 (m, 2H), 7.46-7.38 (m, 4H), ylcarbonyl]piperidin- 7.14-7.07(m, 3H), 4.68 (dd, J = 7.6, 5.7 Hz, 1H), 4- 4.52-4.44 (m, 1H), 4.37 (t,J = 8.3 Hz, 3H), yl}phenyl)azetidine- 4.14-4.05 (m, 1H), 4.02-3.68 (m,7H), 1- 3.17-3.00 (m, 2H), 2.76-2.56 (m, 3H), 2.13-1.91 (m, carboxamide3H), 1.92-1.70 (m, 5H), 1.60-1.31 (m, 3H), 1.26 (d, J = 6.4 Hz, 1H) 55N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆) δ 8.45 (d, J = 2.3 Hz, (ESI(+))(cyclopropylacetyl)piperidin- 1H), 8.40-8.35 (m, 1H), 8.34 (s, 1H), m/e419 4- 7.75 (dt, J = 7.9, 1.9 Hz, 1H), 7.35-7.27 (m, (M + H)⁺yl]phenyl}-3- 3H), 7.03-6.96 (m, 2H), 4.48-4.39 (m, 1H), (pyridin-3-4.26 (t, J = 8.2 Hz, 2H), 3.89-3.71 (m, 4H), yl)azetidine-1- 3.02-2.91(m, 1H), 2.66-2.41 (m, 1H), carboxamide 2.17 (d, J = 6.7 Hz, 2H),1.70-1.59 (m, 2H), 1.48-1.18 (m, 2H), 0.93-0.79 (m, 1H), 0.38-0.27 (m,2H), 0.02 (q, J = 4.8 Hz, 1H) 56 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ8.56 (d, J = 2.3 Hz, (ESI(+)) methylpropanoyl)piperidin- 1H), 8.48 (dd,J = 4.7, 1.6 Hz, 1H), m/e 407 4- 8.44 (s, 1H), 7.86 (dt, J = 7.9, 2.0Hz, 1H), (M + H)⁺ yl]phenyl}-3- 7.47-7.36 (m, 3H), 7.15-7.07 (m, 2H),(pyridin-3- 4.60-4.49 (m, 1H), 4.37 (d, J = 16.2 Hz, 2H),yl)azetidine-1- 4.13-3.81 (m, 4H), 3.20-2.81 (m, 2H), 2.76-2.58 (m,carboxamide 2H), 1.85-1.70 (m, 2H), 1.60-1.28 (m, 2H), 1.09-0.93 (m, 6H)57 N-[4-(1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.3 Hz, (ESI(+))benzoylpiperidin- 1H), 8.48 (dd, J = 4.7, 1.6 Hz, 1H), m/e 4414-yl)phenyl]-3- 8.44 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz, 1H), (M + H)⁺(pyridin-3- 7.52-7.36 (m, 8H), 7.19-7.11 (m, 2H), yl)azetidine-1-4.76-4.48 (m, 1H), 4.37 (d, J = 16.2 Hz, 2H), carboxamide 4.03-3.81 (m,3H), 3.77-3.50 (m, 1H), 3.23-2.63 (m, 3H), 1.97-1.46 (m, 4H) 583-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.56 (d, J = 2.1 Hz,(ESI(+)) N-{4-[1-(3,3,3- 1H), 8.48 (dd, J = 4.8, 1.6 Hz, 1H), m/e 447trifluoropropanoyl)piperidin- 8.44 (s, 1H), 7.86 (dt, J = 7.9, 2.0 Hz,1H), (M + H)⁺ 4- 7.50-7.35 (m, 3H), 7.14-7.07 (m, 2H),yl]phenyl}azetidine- 4.56-4.46 (m, 1H), 4.37 (d, J = 16.2 Hz, 2H), 1-4.03-3.81 (m, 4H), 3.65 (q, J = 11.0 Hz, 1H), carboxamide 3.20-3.04 (m,1H), 2.77-2.57 (m, 2H), 1.82-1.72 (m, 2H), 1.64-1.22 (m, 2H) 643-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.77 (d, J = 2.1 Hz,(ESI(+)) N-{4-[1- 1H), 8.67 (dd, J = 5.2, 1.4 Hz, 1H), m/e 449(tetrahydro-2H- 8.51 (d, J = 2.4 Hz, 1H), 8.29 (dd, J = 8.2, 2.1 Hz,(M + H)⁺ pyran-4- 1H), 7.80-7.71 (m, 1H), 7.46 (dd, J = 8.4, 3.6 Hz,ylacetyl)pyrrolidin- 2H), 7.17 (t, J = 8.6 Hz, 2H), 3- 4.47-4.31 (m,2H), 4.06-3.90 (m, 3H), 3.92-3.72 (m, yl]phenyl}azetidine- 3H),3.69-3.41 (m, 2H), 3.39-3.20 (m, 4H), 1- 2.20 (d, J = 7.5 Hz, 2H),2.05-1.77 (m, 2H), carboxamide 1.65-1.54 (m, 2H), 1.31-1.10 (m, 2H) 65N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.3 Hz, (ESI(+))methylpropanoyl)pyrrolidin- 1H), 8.51-8.45 (m, 2H), 7.86 (dt, J = 7.9,m/e 393 3- 2.0 Hz, 1H), 7.50-7.37 (m, 3H), (M + H)⁺ yl]phenyl}-3-7.23-7.12 (m, 2H), 4.38 (t, J = 8.1 Hz, 2H), (pyridin-3- 4.04-3.79 (m,4H), 3.80-3.64 (m, 1H), yl)azetidine-1- 3.62-3.46 (m, 1H), 3.26-3.03 (m,1H), 2.75-2.62 (m, carboxamide 1H), 2.32-2.10 (m, 1H), 2.08-1.81 (m,1H), 1.05-0.97 (m, 6H) 66 3-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ8.57 (d, J = 2.4 Hz, (ESI(+)) N-(4-{1-[(2S)- 1H), 8.51-8.45 (m, 2H),7.86 (dt, J = 7.9, m/e 421 tetrahydrofuran- 2.0 Hz, 1H), 7.50-7.37 (m,3H), (M + H)⁺ 2- 7.21-7.12 (m, 2H), 4.58-4.48 (m, 1H), 4.38 (t, J = 8.1Hz, ylcarbonyl]pyrrolidin- 2H), 4.07-3.38 (m, 9H), 3- 3.25-3.05 (m, 1H),2.31-2.08 (m, 1H), 2.11-1.71 (m, yl}phenyl)azetidine- 5H) 1- carboxamide67 3-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.4 Hz,(ESI(+)) N-(4-{1-[(2R)- 1H), 8.51-8.45 (m, 2H), 7.86 (dt, J = 7.9, m/e421 tetrahydrofuran- 2.0 Hz, 1H), 7.50-7.37 (m, 3H), (M + H)⁺ 2-7.21-7.12 (m, 2H), 4.58-4.48 (m, 1H), 4.38 (t, J = 8.1 Hz,ylcarbonyl]pyrrolidin- 2H), 4.07-3.38 (m, 9H), 3- 3.25-3.05 (m, 1H),2.31-2.08 (m, 1H), 2.11-1.71 (m, yl}phenyl)azetidine- 5H) 1- carboxamide68 3-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.4 Hz,(ESI(+)) N-{4-[1- 1H), 8.51-8.45 (m, 2H), 7.86 (dt, J = 7.9, m/e 421(tetrahydrofuran- 2.0 Hz, 1H), 7.52-7.37 (m, 3H), (M + H)⁺ 3- 7.23-7.13(m, 2H), 4.38 (t, J = 8.1 Hz, 2H), ylcarbonyl)pyrrolidin- 4.04-3.40 (m,10H), 3.24-2.87 (m, 2H), 3- 2.33-2.11 (m, 1H), 2.12-1.79 (m, 3H)yl]phenyl}azetidine- 1- carboxamide 69 N-{4-[1- ¹H NMR (300 MHz,DMSO-d₆) δ 8.56 (d, J = 2.3 Hz, (ESI(+)) (cyclopropylacetyl)pyrrolidin-1H), 8.51-8.45 (m, 2H), 7.86 (dt, J = 7.9, m/e 405 3- 2.0 Hz, 1H),7.50-7.37 (m, 3H), (M + H)⁺ yl]phenyl}-3- 7.21-7.12 (m, 2H), 4.38 (d, J= 16.3 Hz, 2H), (pyridin-3- 4.04-3.75 (m, 4H), 3.66-3.40 (m, 2H),yl)azetidine-1- 3.24-2.96 (m, 2H), 2.34-2.10 (m, 3H), 2.04-1.80 (m,carboxamide 1H), 1.05-0.92 (m, 1H), 0.50-0.35 (m, 2H), 0.20-0.08 (m, 2H)70 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.4 Hz, (ESI(+))hydroxy-2- 1H), 8.51-8.45 (m, 2H), 7.86 (dt, J = 7.9, m/e 409methylpropanoyl)pyrrolidin- 2.0 Hz, 1H), 7.50-7.38 (m, 3H), (M + H)⁺ 3-7.21-7.13 (m, 2H), 5.14 (d, J = 3.3 Hz, 1H), yl]phenyl}-3- 4.43-4.23 (m,3H), 4.12-3.81 (m, 4H), (pyridin-3- 3.75-3.39 (m, 2H), 2.26-2.06 (m,1H), 1.95-1.75 (m, yl)azetidine-1- 1H), 1.34-1.27 (m, 6H) carboxamide 71N-[4-(1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.76 (bs, 1H), (ESI(+))benzoylpyrrolidin- 8.66 (d, J = 6.2 Hz, 1H), 8.51 (d, J = 8.7 Hz, m/e427 3-yl)phenyl]-3- 1H), 8.31-8.22 (m, 1H), 7.78-7.69 (m, 1H), (M + H)⁺(pyridin-3- 7.60-7.32 (m, 7H), 7.22 (d, J = 8.2 Hz, 1H), yl)azetidine-1-7.14 (d, J = 8.3 Hz, 1H), 4.39 (d, J = 5.1 Hz, carboxamide 1H),4.05-3.87 (m, 4H), 3.74-3.14 (m, 5H), 2.32-2.14 (m, 1H), 2.11-1.87 (m,1H) 72 3-(pyridin-3-yl)- ¹H NMR (400 MHz, DMSO-d₆) δ 8.56 (bs, 1H),(ESI(+)) N-{4-[1-(3,3,3- 8.49 (d, J = 9.5 Hz, 2H), 7.86 (dt, J = 7.9,1.9 Hz, m/e 433 trifluoropropanoyl)pyrrolidin- 1H), 7.51-7.34 (m, 3H),7.17 (dd, J = 8.3, (M + H)⁺ 3- 5.2 Hz, 2H), 4.38 (t, J = 8.3 Hz, 2H),yl]phenyl}azetidine- 4.04-3.75 (m, 4H), 3.74-3.46 (m, 4H), 1- 3.30-3.13(m, 2H), 2.35-2.14 (m, 1H), 2.29-1.81 (m, carboxamide 1H) 73 N-{4-[1- ¹HNMR (300 MHz, DMSO-d₆) δ 8.57 (d, J = 2.4 Hz, (ESI(+))(cyclopropylcarbonyl)pyrrolidin- 1H), 8.51-8.45 (m, 2H), 7.86 (dt, J =7.9, m/e 391 3-yl]phenyl}-3- 1.9 Hz, 1H), 7.51-7.37 (m, 3H), 7.19 (dd,(M + H)⁺ (pyridin-3- J = 12.4, 8.4 Hz, 2H), 4.38 (t, J = 8.1 Hz, 2H),yl)azetidine-1- 4.12-3.75 (m, 5H), 3.71-3.37 (m, 2H), carboxamide3.25-3.04 (m, 2H), 2.34-1.66 (m, 3H), 0.80-0.63 (m, 4H) 74N-(4-{1-[(2S)-2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.75 (bs, 1H), (ESI(+))methylbutanoyl]pyrrolidin- 8.65 (d, J = 5.3 Hz, 1H), 8.51 (d, J = 2.1Hz, m/e 467 3- 1H), 8.24 (dd, J = 8.5, 2.3 Hz, 1H), (M + H)⁺yl}phenyl)-3- 7.76-7.67 (m, 1H), 7.46 (dd, J = 8.5, 3.1 Hz, 2H),(pyridin-3- 7.23-7.12 (m, 2H), 4.47-4.30 (m, 3H), yl)azetidine-1-4.06-3.88 (m, 4H), 3.84-3.43 (m, 2H), 3.43-3.01 (m, carboxamide 2H),2.31-2.11 (m, 1H), 2.07-1.80 (m, 1H), 1.66-1.46 (m, 1H), 1.40-1.20 (m,1H), 1.04-0.95 (m, 3H), 0.88-0.77 (m, 3H) 75 N-[4-(1- (ESI(+))butanoylpyrrolidin- m/e 393 3-yl)phenyl]-3- (M + H)⁺ (pyridin-3-yl)azetidine-1- carboxamide 100 3-(pyridin-3-yl)- ¹H NMR (300 MHz,DMSO-d₆) δ 8.77 (d, J = 2.2 Hz, (ESI(+)) N-{4-[1- 1H), 8.66 (dd, J =5.2, 1.5 Hz, 1H), m/e 435 (tetrahydro-2H- 8.55 (s, 1H), 8.32-8.24 (m,1H), 7.75 (dd, J = 8.0, (M + H)⁺ pyran-4- 5.2 Hz, 1H), 7.54-7.47 (m,2H), ylacetyl)azetidin- 7.30-7.11 (m, 2H), 4.47 (dd, J = 14.6, 6.5 Hz,2H), 3- 4.43-4.32 (m, 1H), 4.30-4.11 (m, 1H), yl]phenyl}azetidine-4.12-3.92 (m, 4H), 3.86-3.65 (m, 4H), 3.34-3.22 (m, 1- 2H), 2.06-1.83(m, 3H), 1.63-1.52 (m, 2H), carboxamide 1.29-1.06 (m, 2H) 101N-{4-[1-(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))methylpropanoyl)azetidin- δ 8.73 (d, J = 2.2 Hz, 1H), 8.64 (dd, J = 5.3,m/e 379 3- 1.4 Hz, 1H), 8.31-8.24 (m, 1H), 7.77 (dd, (M + H)⁺yl]phenyl}-3- J = 8.0, 5.3 Hz, 1H), 7.50-7.44 (m, 2H), (pyridin-3-7.24-7.18 (m, 2H), 4.51-4.15 (m, 4H), yl)azetidine-1- 4.15-3.72 (m, 6H),3.89-3.70 (m, 1H), 1.02 (d, J = 6.8 Hz, carboxamide 6H) 1023-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.78 (d, J = 2.1 Hz,(ESI(+)) N-(4-{1-[(2S)- 1H), 8.68 (dd, J = 5.2, 1.4 Hz, 1H), m/e 407tetrahydrofuran- 8.55 (s, 1H), 8.30 (d, J = 8.6 Hz, 1H), 7.77 (dd, J =8.0, (M + H)⁺ 2- 5.2 Hz, 1H), 7.52 (t, J = 9.0 Hz, 2H),ylcarbonyl]azetidin- 7.27-7.20 (m, 2H), 4.67-4.55 (m, 1H), 3- 4.45-4.30(m, 3H), 4.31-4.11 (m, 3H), 4.07-3.93 (m, yl}phenyl)azetidine- 4H),3.86-3.65 (m, 1H), 2.11-1.92 (m, 2H), 1- 1.92-1.74 (m, 3H) carboxamide103 3-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.76 (t, J = 6.1 Hz,(ESI(+)) N-(4-{1-[(2R)- 1H), 8.66 (dt, J = 9.5, 4.8 Hz, 1H), m/e 407tetrahydrofuran- 8.57 (d, J = 10.0 Hz, 1H), 8.28 (d, J = 8.1 Hz, 1H),(M + H)⁺ 2- 7.75 (dd, J = 7.9, 5.3 Hz, 1H), 7.50 (d, J = 8.4 Hz,ylcarbonyl]azetidin- 2H), 7.23 (d, J = 8.3 Hz, 2H), 3- 4.69-4.46 (m,1H), 4.47-4.29 (m, 3H), 4.31-4.09 (m, yl}phenyl)azetidine- 3H),4.08-3.88 (m, 3H), 3.88-3.58 (m, 3H), 1- 2.29-1.72 (m, 4H) carboxamide104 3-(pyridin-3-yl)- ¹H NMR (300 MHz, DMSO-d₆) δ 8.75 (d, J = 2.0 Hz,(ESI(+)) N-{4-[1- 1H), 8.64 (dd, J = 5.2, 1.4 Hz, 1H), m/e 407(tetrahydrofuran- 8.55 (s, 1H), 8.23 (d, J = 8.0 Hz, 1H), 7.71 (dd, J =8.0, (M + H)⁺ 3- 5.2 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H),ylcarbonyl)azetidin- 7.24 (d, J = 8.4 Hz, 2H), 4.53 (dd, J = 15.0, 8.1Hz, 3- 2H), 4.47-4.33 (m, 2H), 4.16 (ddd, J = 14.1, yl]phenyl}azetidine-10.1, 4.6 Hz, 3H), 4.08-3.93 (m, 3H), 1- 3.91-3.71 (m, 3H), 3.71-3.56(m, 2H), carboxamide 3.14-2.93 (m, 1H), 2.10-1.87 (m, 2H) 105 N-{4-[1-¹H NMR (300 MHz, DMSO-d₆) δ 8.71 (d, J = 1.9 Hz, (ESI(+))(cyclopropylacetyl)azetidin- 1H), 8.61 (dd, J = 5.1, 1.5 Hz, 1H), m/e391 3- 8.54 (s, 1H), 8.17 (d, J = 8.0 Hz, 1H), 7.66 (dd, J = 8.0, (M +H)⁺ yl]phenyl}-3- 5.1 Hz, 1H), 7.53-7.47 (m, 2H), 7.23 (d, J = 8.5 Hz,(pyridin-3- 2H), 4.53-4.31 (m, 2H), 4.20 (dd, J = 14.1, yl)azetidine-1-6.7 Hz, 1H), 4.09-3.90 (m, 2H), carboxamide 3.85-3.42 (m, 2H), 2.11 (d,J = 7.0 Hz, 2H), 2.03 (d, J = 6.8 Hz, 1H), 1.00-0.86 (m, 1H), 0.49-0.36(m, 3H), 0.18-0.07 (m, 3H) 106 N-{4-[1-(2- ¹H NMR (300 MHz, DMSO-d₆) δ8.75 (d, J = 2.2 Hz, (ESI(+)) hydroxy-2- 1H), 8.64 (dd, J = 5.2, 1.5 Hz,1H), m/e 395 methylpropanoyl)azetidin- 8.54 (s, 1H), 8.27-8.20 (m, 1H),7.71 (dd, J = 8.0, (M + H)⁺ 3- 5.2 Hz, 1H), 7.57-7.40 (m, 2H),yl]phenyl}-3- 7.28-7.14 (m, 2H), 4.86-4.65 (m, 2H), 4.45-4.30 (m,(pyridin-3- 3H), 4.21 (d, J = 8.2 Hz, 1H), 4.09-3.86 (m, yl)azetidine-1-3H), 3.87-3.57 (m, 2H), 1.27 (s, 6H) carboxamide 107 N-[4-(1- ¹H NMR(300 MHz, DMSO-d₆) δ 8.76 (d, J = 2.1 Hz, (ESI(+)) benzoylazetidin- 1H),8.66 (dd, J = 5.2, 1.5 Hz, 1H), m/e 413 3-yl)phenyl]-3- 8.55 (s, 1H),8.30-8.22 (m, 1H), 7.77-7.64 (m, (M + H)⁺ (pyridin-3- 3H), 7.57-7.41 (m,5H), 7.32-7.09 (m, 2H), yl)azetidine-1- 4.65 (t, J = 8.7 Hz, 2H),4.50-4.31 (m, 3H), carboxamide 4.28 (d, J = 7.1 Hz, 1H), 4.00 (q, J =5.6 Hz, 3H), 3.91-3.71 (m, 1H) 108 3-(pyridin-3-yl)- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) N-{4-[1-(3,3,3- δ 8.69 (d, J = 2.2Hz, 1H), 8.63-8.54 (m, m/e 419 trifluoropropanoyl)azetidin- 1H),8.24-7.99 (m, 1H), 7.77-7.55 (m, 1H), (M + H)⁺ 3- 7.55-7.44 (m, 2H),7.30-7.19 (m, 2H), yl]phenyl}azetidine- 4.62-4.24 (m, 6H), 4.21-3.63 (m,6H) 1- carboxamide 109 N-{4-[1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.76 (d, J =2.2 Hz, (ESI(+)) (cyclopropylcarbonyl)azetidin- 1H), 8.66 (dd, J = 5.2,1.5 Hz, 1H), m/e 377 3- 8.55 (s, 1H), 8.30-8.22 (m, 1H), 7.73 (dd, J =8.0, (M + H)⁺ yl]phenyl}-3- 5.2 Hz, 1H), 7.55-7.48 (m, 2H), (pyridin-3-7.33-7.11 (m, 2H), 4.62 (t, J = 8.1 Hz, 1H), yl)azetidine-1- 4.54-4.31(m, 2H), 4.32-4.09 (m, 2H), 3.93 (dq, J = 10.9, carboxamide 5.1 Hz, 2H),3.92-3.61 (m, 2H), 1.63-1.51 (m, 1H), 0.73 (d, J = 2.0 Hz, 2H) 110N-(4-{1-[(2S)-2- ¹H NMR (300 MHz, DMSO-d₆) δ (ESI(+))methylbutanoyl]azetidin- 8.78-8.68 (m, 1H), 8.67-8.61 (m, 1H), 8.54 (s,1H), m/e 393 3- 8.27-8.19 (m, 1H), 7.75-7.67 (m, 1H), (M + H)⁺yl}phenyl)-3- 7.54-7.47 (m, 2H), 7.33-7.14 (m, 2H), 4.99 (bs, 3H),(pyridin-3- 4.56-4.12 (m, 2H), 4.11-3.88 (m, 3H), yl)azetidine-1-3.84-3.75 (m, 2H), 2.36-2.22 (m, 1H), carboxamide 1.60-1.43 (m, 1H),1.39-1.17 (m, 1H), 1.02-0.95 (m, 3H), 0.84 (t, J = 7.4 Hz, 3H) 111N-[4-(1- ¹H NMR (300 MHz, DMSO-d₆) δ 8.75 (d, J = 2.2 Hz, (ESI(+))butanoylazetidin- 1H), 8.65 (dd, J = 5.2, 1.5 Hz, 1H), m/e 3793-yl)phenyl]-3- 8.55 (s, 1H), 8.24 (dt, J = 8.0, 1.8 Hz, 1H), 7.72 (dd,(M + H)⁺ (pyridin-3- J = 8.0, 5.2 Hz, 1H), 7.54-7.47 (m, 2H),yl)azetidine-1- 7.20 (dd, J = 16.0, 8.6 Hz, 2H), 4.52-4.33 (m, 2H),carboxamide 4.26-4.15 (m, 1H), 4.11-3.94 (m, 3H), 3.82-3.66 (m, 2H),2.06 (t, J = 7.3 Hz, 2H), 1.59-1.50 (m, 1H), 1.52-1.43 (m, 2H),1.02-0.74 (m, 4H) 156 3-(2- ¹H NMR (300 MHz, DMSO-d₆) δ 8.44 (s, 1H),(ESI(+)) fluoropyridin-3- 8.14 (dt, J = 4.8, 1.5 Hz, 1H), 8.09-7.98 (m,m/e 441 yl)-N-{4-[1-(2- 1H), 7.49-7.34 (m, 3H), 7.14-7.06 (m, 2H), (M +H)⁺ hydroxy-2- 5.35 (s, 1H), 4.73 (bs, 1H), 4.39-4.28 (m, 2H),methylpropanoyl)piperidin- 4.08-3.92 (m, 4H), 3.23-2.59 (m, 3H), 4-1.80-1.70 (m, 2H), 1.71-1.36 (m, 2H), 1.33 (s, 6H) yl]phenyl}azetidine-1- carboxamide 159 3-(pyridin-3-yl)- ¹H NMR (500 MHz, DMSO-d₆) δ 8.57(d, J = 2.3 Hz, (ESI(+)) N-(4-{1-[(3S)- 1H), 8.49 (dd, J = 4.8, 1.6 Hz,1H), m/e 435 tetrahydrofuran- 8.47 (s, 1H), 7.88 (dt, J = 7.9, 1.9 Hz,1H), (M + H)⁺ 3- 7.46-7.40 (m, 3H), 7.11 (d, J = 8.6 Hz, 2H),ylcarbonyl]piperidin- 4.57-4.50 (m, 1H), 4.37 (t, J = 8.3 Hz, 2H), 4-4.09-4.02 (m, 1H), 3.98-3.92 (m, 2H), yl}phenyl)azetidine- 3.93-3.79 (m,2H), 3.81-3.52 (m, 2H), 3.16-3.04 (m, 1- 1H), 2.75-2.65 (m, 1H), 2.60(d, J = 7.6 Hz, carboxamide 1H), 2.10-1.94 (m, 2H), 1.83-1.72 (m, 2H),1.59-1.32 (m, 2H), 1.34-1.21 (m, 2H) 160 3-(4- ¹H NMR (500 MHz, DMSO-d₆)δ 8.70 (s, 1H), (ESI(+)) chloropyridin-3- 8.58-8.38 (m, 2H), 7.57 (d, J= 5.2 Hz, 1H), m/e 469 yl)-N-(4-{1- 7.44-7.39 (m, 2H), 7.14-7.08 (m,2H), (M + H)⁺ [(3S)- 4.57-4.50 (m, 1H), 4.45-4.33 (m, 2H),tetrahydrofuran- 4.20-4.00 (m, 4H), 3.88 (dt, J = 12.2, 8.1 Hz, 1H), 3-3.78-3.63 (m, 3H), 3.20-3.04 (m, 1H), ylcarbonyl]piperidin- 2.75-2.56(m, 2H), 2.10-1.94 (m, 2H), 1.82-1.71 (m, 4- 2H), 1.56-1.32 (m, 2H)yl}phenyl)azetidine- 1- carboxamide 161 3-(2- ¹H NMR (500 MHz, DMSO-d₆)δ 8.46 (s, 1H), (ESI(+)) chloropyridin-3- 8.41-8.30 (m, 1H), 8.01 (dd, J= 7.7, 1.8 Hz, m/e 457 yl)-N-{4-[1-(2- 1H), 7.56-7.43 (m, 1H), 7.44-7.39(m, 2H), (M + H)⁺ hydroxy-2- 7.13-7.07 (m, 2H), 5.37 (s, 1H),methylpropanoyl)piperidin- 5.03-4.45 (m, 2H), 4.42-4.30 (m, 2H),4.12-3.99 (m, 4- 3H), 3.29-2.58 (m, 3H), 1.79-1.72 (m, 2H),yl]phenyl}azetidine- 1.63-1.40 (m, 2H), 1.33 (s, 6H) 1- carboxamide 163N-[4-(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))pentanoylpiperidin- ppm 8.88 (s, 1 H) 8.78 (d, J = 5.19 Hz, 1 m/e 4214-yl)phenyl]-3- H) 8.60 (d, J = 8.24 Hz, 1 H) 8.02 (dd, J = 7.93, (M +H)⁺ (pyridin-3- 5.80 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.12 (d,yl)azetidine-1- J = 8.54 Hz, 2 H) 4.52 (d, J = 12.82 Hz, 1 H)carboxamide 4.42 (t, J = 8.09 Hz, 2 H) 3.94-4.13 (m, 4 H) 3.09 (t, J =12.21 Hz, 1 H) 2.54-2.76 (m, 2 H) 2.33 (t, 2 H) 1.72-1.82 (m, 2 H)1.41-1.55 (m, 3 H) 1.25-1.41 (m, 3 H) 0.89 (t, J = 7.32 Hz, 3 H) 164N-(4-{1-[(2- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))methylcyclopropyl)carbonyl]piperidin- ppm 8.87 (s, 1 H) 8.76 (d, J =5.49 Hz, 1 m/e 419 4- H) 8.56 (d, J = 7.93 Hz, 1 H) 7.99 (dd, J = 8.09,(M + H)⁺ yl}phenyl)-3- 5.65 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.13 (d,(pyridin-3- J = 8.54 Hz, 2 H) 4.28-4.54 (m, 4 H) yl)azetidine-1-3.98-4.13 (m, 3 H) 3.09-3.22 (m, 1 H) 2.73 (t, J = 11.90 Hz, carboxamide1 H) 2.66 (t, 1 H) 1.68-1.92 (m, 3 H) 1.32-1.58 (m, 2 H) 1.10-1.24 (m, 1H) 1.04-1.09 (m, 3 H) 0.89-1.00 (m, J = 31.89, 6.26 Hz, 1 H) 0.53-0.59(m, 1 H) 165 N-(4-{1- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.)(ESI(+)) [(1S,4R)- ppm 8.88 (s, 1 H) 8.77 (d, J = 5.19 Hz, 1 m/e 473bicyclo[2.2.1]hept- H) 8.58 (d, J = 7.94 Hz, 1 H) 8.01 (dd, J = 7.93,(M + H)⁺ 2- 5.49 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.12 (d,ylacetyl]piperidin- J = 8.24 Hz, 2 H) 4.52 (d, J = 12.82 Hz, 1 H)4-yl}phenyl)-3- 4.42 (t, J = 8.09 Hz, 2 H) 3.97-4.12 (m, 4 H) 3.08 (t,(pyridin-3- J = 12.05 Hz, 1 H) 2.65-2.76 (m, 1 H) yl)azetidine-1-2.54-2.62 (m, 1 H) 2.32 (dd, J = 15.26, 7.93 Hz, 1 H) carboxamide2.12-2.21 (m, 2 H) 1.95 (d, J = 4.58 Hz, 1 H) 1.71-1.84 (m, 3 H)1.31-1.55 (m, 6 H) 0.98-1.21 (m, 4 H) 166 N-{4-[1-(4- ¹H NMR (500 MHz,DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) methylpentanoyl)piperidin- ppm 8.88(s, 1 H) 8.77 (d, J = 5.49 Hz, 1 m/e 435 4- H) 8.58 (d, J = 7.93 Hz, 1H) 8.01 (dd, J = 7.93, (M + H)⁺ yl]phenyl}-3- 5.80 Hz, 1 H) 7.41 (d, J =8.54 Hz, 2 H) 7.11 (d, (pyridin-3- 2 H) 4.52 (d, J = 12.82 Hz, 1 H) 4.42(t, J = 8.09 Hz, yl)azetidine-1- 2 H) 3.93-4.13 (m, 4 H) 3.04-3.15 (m, 1carboxamide H) 2.66-2.75 (m, 1 H) 2.55-2.62 (m, 1 H) 2.30-2.36 (m, 2H)1.78 (dd, J = 25.02, 12.82 Hz, 2 H) 1.45-1.63 (m, 2 H) 1.30-1.46 (m, 3H) 0.88 (d, J = 6.41 Hz, 6 H) 167 N-{4-[1-(3- ¹H NMR (500 MHz,DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) methylpentanoyl)piperidin- ppm 8.88(s, 1 H) 8.77 (d, J = 5.49 Hz, 1 m/e 435 4- H) 8.58 (d, J = 8.24 Hz, 1H) 8.01 (dd, J = 7.93, (M + H)⁺ yl]phenyl}-3- 5.49 Hz, 1 H) 7.41 (d, J =8.54 Hz, 2 H) 7.12 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.55 (d, J = 12.82Hz, 1 H) yl)azetidine-1- 4.42 (t, J = 8.09 Hz, 2 H) 3.96-4.13 (m, 4 H)3.10 (t, carboxamide J = 12.21 Hz, 1 H) 2.66-2.76 (m, 1 H) 2.55-2.62 (m,1 H) 2.28-2.35 (m, 1 H) 2.11-2.20 (m, 1 H) 1.72-1.85 (m, 3 H) 1.42-1.56(m, 1 H) 1.30-1.41 (m, 2 H) 1.09-1.24 (m, 1 H) 0.83-0.91 (m, 6 H) 168N-{4-[1-(3- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))ethoxypropanoyl)piperidin- ppm 8.88 (s, 1 H) 8.77 (d, J = 5.19 Hz, 1 m/e437 4- H) 8.58 (d, J = 8.24 Hz, 1 H) 8.01 (dd, J = 7.93, (M + H)⁺yl]phenyl}-3- 5.80 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.12 (d,(pyridin-3- J = 8.54 Hz, 2 H) 4.52 (d, J = 12.82 Hz, 1 H)yl)azetidine-1- 4.42 (t, J = 8.24 Hz, 2 H) 3.97-4.15 (m, 4 H) 3.61 (t,carboxamide J = 6.71 Hz, 2 H) 3.43 (q, J = 7.02 Hz, 2 H) 3.09 (t, J =12.05 Hz, 1 H) 2.66-2.78 (m, 1 H) 2.54-2.66 (m, 3 H) 1.71-1.81 (m, 2 H)1.47-1.58 (m, 1 H) 1.30-1.43 (m, 1 H) 1.10 (t, J = 7.02 Hz, 3 H) 169N-{4-[1-(2,2- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))dimethylbutanoyl)piperidin- ppm 8.85 (s, 1 H) 8.75 (d, J = 5.19 Hz, 1m/e 435 4- H) 8.53 (d, J = 7.93 Hz, 1 H) 7.97 (dd, J = 8.09, (M + H)⁺yl]phenyl}-3- 5.65 Hz, 1 H) 7.39-7.44 (m, 2 H) 7.12 (d, (pyridin-3- J =8.54 Hz, 2 H) 4.41 (t, J = 7.93 Hz, 4 H) yl)azetidine-1- 3.99-4.10 (m, 3H) 2.85 (t, J = 12.97 Hz, 2 H) carboxamide 2.68-2.77 (m, 1 H) 1.80 (d, J= 12.82 Hz, 2 H) 1.57-1.67 (m, 2 H) 1.34-1.49 (m, 2 H) 1.17 (s, 6 H)0.83 (t, J = 7.32 Hz, 3 H) 170 N-{4-[1-(3,3- ¹H NMR (500 MHz,DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) dimethylbutanoyl)piperidin- ppm 8.87(s, 1 H) 8.76 (d, J = 5.49 Hz, 1 m/e 435 4- H) 8.56 (d, J = 7.93 Hz, 1H) 7.99 (dd, J = 8.09, (M + H)⁺ yl]phenyl}-3- 5.65 Hz, 1 H) 7.41 (d, J =8.54 Hz, 2 H) 7.12 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.60 (d, J = 13.12Hz, 1 H) yl)azetidine-1- 4.42 (t, J = 8.09 Hz, 2 H) 4.00-4.13 (m, 4 H)3.09 (t, carboxamide J = 12.05 Hz, 1 H) 2.67-2.77 (m, 1 H) 2.54-2.61 (m,1 H) 2.17-2.36 (m, 2 H) 1.78 (t, J = 12.66 Hz, 2 H) 1.31-1.55 (m, 2 H)1.00 (s, 9 H) 171 N-{4-[1-(2,2- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25°C.) (ESI(+)) dimethylpropanoyl)piperidin- ppm 8.86 (s, 1 H) 8.76 (d, J =5.49 Hz, 1 m/e 421 4- H) 8.50-8.62 (m, 1 H) 7.94-7.99 (m, 1 H) (M + H)⁺yl]phenyl}-3- 7.41 (d, J = 8.54 Hz, 2 H) 7.13 (d, J = 8.54 Hz, 2(pyridin-3- H) 4.41 (t, J = 7.93 Hz, 4 H) 3.99-4.12 (m, 3 H)yl)azetidine-1- 2.80-2.97 (m, 2 H) 2.66-2.78 (m, 1 H) carboxamide 1.79(d, J = 12.82 Hz, 2 H) 1.37-1.51 (m, 2 H) 1.22 (s, 9 H) 172 N-[4-(1- ¹HNMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) butanoylpiperidin- ppm8.88 (s, 1 H) 8.78 (d, J = 5.49 Hz, 1 m/e 407 4-yl)phenyl]-3- H) 8.59(d, J = 8.24 Hz, 1 H) 8.01 (dd, J = 8.09, (M + H)⁺ (pyridin-3- 5.65 Hz,1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.12 (d, yl)azetidine-1- J = 8.54 Hz, 2H) 4.53 (d, J = 13.12 Hz, 1 H) carboxamide 4.42 (t, J = 8.24 Hz, 2 H)3.96-4.13 (m, 4 H) 3.09 (t, J = 12.05 Hz, 1 H) 2.66-2.76 (m, 1 H)2.55-2.63 (m, 1 H) 2.32 (t, J = 7.32 Hz, 2 H) 1.71-1.90 (m, 2 H)1.42-1.59 (m, 3 H) 1.32-1.43 (m, 1 H) 0.90 (t, J = 7.32 Hz, 3 H) 173N-{4-[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))(ethoxyacetyl)piperidin- ppm 8.88 (s, 1 H) 8.77 (d, J = 5.49 Hz, 1 m/e423 4- H) 8.59 (d, J = 8.24 Hz, 1 H) 8.01 (dd, J = 8.09, (M + H)⁺yl]phenyl}-3- 5.65 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.12 (d,(pyridin-3- J = 8.54 Hz, 2 H) 4.38-4.51 (m, 3 H) yl)azetidine-1-3.88-4.20 (m, 6 H) 3.43-3.54 (m, 2 H) 3.07 (t, J = 12.21 Hz, carboxamide1 H) 2.60-2.78 (m, 2 H) 1.78 (d, J = 12.51 Hz, 2 H) 1.33-1.60 (m, 2 H)1.14 (t, J = 7.02 Hz, 3 H) 174 N-{4-[1-(3- ¹H NMR (500 MHz, DMSO-d₆/D₂OTemp = 25° C.) (ESI(+)) methylbutanoyl)piperidin- ppm 8.88 (s, 1 H) 8.78(d, J = 5.19 Hz, 1 m/e 421 4- H) 8.60 (d, J = 8.24 Hz, 1 H) 8.02 (dd, J= 8.09, (M + H)⁺ yl]phenyl}-3- 5.65 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H)7.12 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.54 (d, J = 13.12 Hz, 1 H)yl)azetidine-1- 4.42 (t, J = 8.24 Hz, 2 H) 3.96-4.14 (m, 4 H) 3.09 (t,carboxamide J = 12.05 Hz, 1 H) 2.66-2.76 (m, 1 H) 2.55-2.63 (m, 1 H)2.17-2.27 (m, 2 H) 1.94-2.04 (m, 1 H) 1.76 (d, J = 17.09 Hz, 2H)1.32-1.53 (m, 2 H) 0.92 (dd, J = 6.56, 1.98 Hz, 6 H) 175 N-{4-[1-(N- ¹HNMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) acetyl-L- ppm 8.89 (s,1 H) 8.79 (d, J = 5.49 Hz, 1 m/e 492 leucyl)piperidin- H) 8.62 (d, J =8.24 Hz, 1 H) 8.03 (dd, J = 7.93, (M + H)⁺ 4-yl]phenyl}-3- 5.80 Hz, 1 H)7.42 (d, J = 8.54 Hz, 2 H) 7.12 (dd, (pyridin-3- J = 11.29, 8.54 Hz, 2H) 4.80 (dd, J = 9.77, 4.58 Hz, yl)azetidine-1- 1 H) 4.49 (d, 1 H) 4.42(t, J = 8.24 Hz, 2 H) carboxamide 3.97-4.17 (m, 4 H) 3.11-3.20 (m, 1 H)2.74 (t, J = 11.90 Hz, 1 H) 2.65 (t, J = 11.75 Hz, 1 H) 1.85 (d, J =4.88 Hz, 3 H) 1.78 (t, J = 13.73 Hz, 2 H) 1.27-1.65 (m, 5 H) 0.84-0.94(m, 6 H) 176 N-(4-{1-[(2- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.)(ESI(+)) methoxyethoxy)acetyl]piperidin- ppm 8.88 (s, 1 H) 8.77 (d, J =5.49 Hz, 1 m/e 453 4- H) 8.58 (d, J = 8.24 Hz, 1 H) 8.01 (dd, J = 8.09,(M + H)⁺ yl}phenyl)-3- 5.65 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.12 (d,(pyridin-3- J = 8.54 Hz, 2 H) 4.37-4.51 (m, 3 H) yl)azetidine-1-3.99-4.25 (m, 5 H) 3.89 (d, J = 12.82 Hz, 1 H) carboxamide 3.51-3.64 (m,2 H) 3.44-3.50 (m, 2 H) 3.24-3.29 (m, 3 H) 3.07 (t, J = 12.21 Hz, 1 H)2.59-2.79 (m, 2 H) 1.77 (d, J = 12.51 Hz, 2 H) 1.47-1.64 (m, 1 H)1.31-1.48 (m, 1 H) 177 N-{4-[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25°C.) (ESI(+)) (cyclohexylcarbonyl)piperidin- ppm 8.85 (s, 1 H) 8.75 (d, J= 5.19 Hz, 1 m/e 447 4- H) 8.53 (d, J = 8.24 Hz, 1 H) 7.97 (dd, J =8.09, (M + H)⁺ yl]phenyl}-3- 5.65 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H)7.13 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.53 (d, 1 H) 4.41 (t, J = 7.93Hz, yl)azetidine-1- 2 H) 3.98-4.11 (m, 4 H) 2.98-3.16 (m, 1 carboxamideH) 2.64-2.75 (m, 1 H) 2.58-2.63 (m, 2 H) 1.64 (d, J = 9.77 Hz, 7 H)1.05-1.53 (m, 7 H) 178 N-{4-[1- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25°C.) (ESI(+)) (cyclohexylacetyl)piperidin- ppm 8.83 (s, 1 H) 8.73 (d, J =5.19 Hz, 1 m/e 461 4- H) 8.48 (d, J = 7.94 Hz, 1 H) 7.93 (dd, J = 7.93,(M + H)⁺ yl]phenyl}-3- 5.49 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.12 (d,(pyridin-3- J = 8.54 Hz, 2 H) 4.54 (d, J = 13.12 Hz, 1 H)yl)azetidine-1- 4.36-4.45 (m, 2 H) 3.92-4.13 (m, 4 H) 3.09 (t,carboxamide J = 12.05 Hz, 1 H) 2.66-2.78 (m, 1 H) 2.56-2.65 (m, 1 H)2.22 (d, J = 6.71 Hz, 2 H) 1.55-1.91 (m, 8 H) 1.30-1.54 (m, 2 H)1.05-1.28 (m, 3 H) 0.88-0.99 (m, J = 11.90, 11.90 Hz, 2 H) 1793-(pyridin-3-yl)- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))N-{4-[1-(4,4,4- ppm 8.88 (s, 1 H) 8.77 (d, J = 5.49 Hz, 1 m/e 461trifluorobutanoyl)piperidin- H) 8.58 (d, J = 8.24 Hz, 1 H) 8.01 (dd, J =8.09, (M + H)⁺ 4- 5.65 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.13 (d,yl]phenyl}azetidine- J = 8.85 Hz, 2 H) 4.52 (d, J = 12.82 Hz, 1 H) 1-4.42 (t, J = 8.24 Hz, 2 H) 3.93-4.13 (m, 4 H) 3.11 (t, carboxamide J =12.05 Hz, 1 H) 2.54-2.76 (m, 5 H) 2.43-2.50 (m, 1 H) 1.77 (t, J = 11.90Hz, 2 H) 1.34-1.63 (m, 2 H) 180 N-{4-[1- ¹H NMR (500 MHz, DMSO-d₆/D₂OTemp = 25° C.) (ESI(+)) (cyclopentylcarbonyl)piperidin- ppm 8.89 (s, 1H) 8.78 (d, J = 5.49 Hz, 1 m/e 433 4- H) 8.56-8.63 (m, 1 H) 8.03 (dd, J= 8.09, 5.65 Hz, (M + H)⁺ yl]phenyl}-3- 1 H) 7.41 (d, J = 8.54 Hz, 2 H)7.13 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.53 (d, J = 12.82 Hz, 1 H)yl)azetidine-1- 4.42 (t, J = 8.24 Hz, 2 H) 4.00-4.15 (m, 4 H)carboxamide 2.95-3.15 (m, 2 H) 2.67-2.76 (m, 1 H) 2.57-2.65 (m, 1 H)1.29-1.86 (m, 12 H) 181 N-(4-{1-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp =25° C.) (ESI(+)) methylcyclohexyl)carbonyl]piperidin- ppm 8.85 (s, 1 H)8.75 (d, J = 5.49 Hz, 1 m/e 461 4-yl}phenyl)- H) 8.54 (d, J = 7.93 Hz, 1H) 7.97 (dd, J = 7.93, (M + H)⁺ 3-(pyridin-3- 5.49 Hz, 1 H) 7.41 (d, J =8.24 Hz, 2 H) 7.12 (d, yl)azetidine-1- J = 8.54 Hz, 2 H) 4.41 (t, J =7.93 Hz, 4 H) carboxamide 3.97-4.18 (m, 3 H) 2.67-2.97 (m, 3 H) 1.97 (d,J = 7.93 Hz, 2 H) 1.79 (d, J = 12.21 Hz, 2 H) 1.25-1.57 (m, 10 H) 1.20(s, 3 H) 182 N-{4-[1-(furan-3- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25°C.) (ESI(+)) ylcarbonyl)piperidin- ppm 8.88 (s, 1 H) 8.77 (d, J = 5.49Hz, 1 m/e 431 4-yl]phenyl}- H) 8.58 (d, J = 7.93 Hz, 1 H) 7.97-8.05 (m,2 H) (M + H)⁺ 3-(pyridin-3- 7.68-7.79 (m, 1 H) 7.42 (d, J = 8.54 Hz, 2H) yl)azetidine-1- 7.15 (d, J = 8.54 Hz, 2 H) 6.68 (s, 1 H) 4.57 (s, 1carboxamide H) 4.42 (t, J = 8.24 Hz, 2 H) 3.99-4.15 (m, 4 H) 3.17 (s, 1H) 2.63-2.87 (m, 2 H) 1.80 (s, 2 H) 1.55 (s, 2 H) 183 N-[4-(1- ¹H NMR(500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) acetylpiperidin-4- ppm8.88 (s, 1 H) 8.78 (d, J = 5.49 Hz, 1 m/e 379 yl)phenyl]-3- H) 8.60 (d,J = 7.94 Hz, 1 H) 8.02 (dd, J = 8.09, (M + H)⁺ (pyridin-3- 5.65 Hz, 1 H)7.41 (d, J = 8.54 Hz, 2 H) 7.13 (d, yl)azetidine-1- J = 8.54 Hz, 2 H)4.50 (d, J = 13.12 Hz, 1 H) carboxamide 4.42 (t, J = 8.24 Hz, 2 H)4.00-4.14 (m, 3 H) 3.91 (d, J = 13.73 Hz, 1 H) 3.06-3.17 (m, 1 H)2.63-2.74 (m, 1 H) 2.56-2.64 (m, 1 H) 2.04 (s, 3 H) 1.76 (t, J = 15.56Hz, 2H) 1.47-1.60 (m, 1 H) 1.32-1.45 (m, 1 H) 184 N-{4-[1- ¹H NMR (500MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) (methoxyacetyl)piperidin- ppm8.88 (s, 1 H) 8.78 (d, J = 5.49 Hz, 1 m/e 409 4- H) 8.60 (d, J = 8.24Hz, 1 H) 8.02 (dd, J = 8.09, (M + H)⁺ yl]phenyl}-3- 5.65 Hz, 1 H) 7.41(d, J = 8.54 Hz, 2 H) 7.13 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.36-4.55(m, 3 H) yl)azetidine-1- 3.97-4.20 (m, 5 H) 3.85 (d, J = 13.43 Hz, 1 H)3.30 (s, 3 H) carboxamide 3.07 (t, J = 12.36 Hz, 1 H) 2.57-2.78 (m, 2 H)1.77 (d, J = 12.51 Hz, 2 H) 1.34-1.61 (m, 2 H) 185 3-(pyridin-3-yl)- ¹HNMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) N-{4-[1- ppm 8.86 (s,1 H) 8.75 (d, J = 5.19 Hz, 1 m/e 447 (thiophen-3- H) 8.54 (d, J = 8.24Hz, 1 H) 7.97 (dd, J = 8.09, (M + H)⁺ ylcarbonyl)piperidin- 5.65 Hz, 1H) 7.77 (d, J = 1.83 Hz, 1 H) 7.61 (dd, 4- J = 4.88, 3.05 Hz, 1 H) 7.43(d, 2 H) yl]phenyl}azetidine- 7.20-7.25 (m, 1 H) 7.16 (d, J = 8.54 Hz, 2H) 4.58 (s, 1 H) 1- 4.42 (t, J = 7.93 Hz, 2 H) 3.99-4.14 (m, 3 H)carboxamide 3.84-3.95 (m, 1 H) 3.14-3.27 (m, 1 H) 2.69-2.94 (m, 2 H)1.67-1.97 (m, J = 17.09 Hz, 2 H) 1.46-1.64 (m, 2 H) 186 N-(4-{1-[(3- ¹HNMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) methylthiophen- ppm8.87 (s, 1 H) 8.76 (d, J = 5.19 Hz, 1 m/e 461 2- H) 8.56 (d, J = 8.24Hz, 1 H) 7.99 (dd, J = 7.93, (M + H)⁺ yl)carbonyl]piperidin- 5.49 Hz, 1H) 7.55 (d, J = 5.19 Hz, 1 H) 7.42 (d, 4- J = 8.85 Hz, 2 H) 7.14 (d, J =8.54 Hz, 2 H) yl}phenyl)-3- 6.95 (d, J = 4.88 Hz, 1 H) 4.42 (t, J = 8.09Hz, 2 H) (pyridin-3- 3.98-4.31 (m, 5 H) 3.04 (d, J = 6.10 Hz, 2 H)yl)azetidine-1- 2.70-2.84 (m, 1 H) 2.21 (s, 3 H) 1.82 (d, carboxamide J= 12.51 Hz, 2 H) 1.42-1.56 (m, 2 H) 187 N-{4-[1- ¹H NMR (500 MHz,DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) (morpholin-4- ppm 8.86 (s, 1 H) 8.76(d, J = 5.49 Hz, 1 m/e 464 ylacetyl)piperidin- H) 8.54 (d, J = 7.93 Hz,1 H) 7.98 (dd, J = 8.09, (M + H)⁺ 4-yl]phenyl}-3- 5.65 Hz, 1 H) 7.43 (d,J = 8.54 Hz, 2 H) 7.13 (d, (pyridin-3- J = 8.55 Hz, 2 H) 4.27-4.54 (m, 5H) yl)azetidine-1- 3.92-4.12 (m, 6 H) 3.78-3.88 (m, 2 H) 3.38-3.53 (m, 2carboxamide H) 3.10-3.23 (m, 3 H) 2.77 (t, J = 12.05 Hz, 2 H) 1.83 (d, J= 13.12 Hz, 2 H) 1.55-1.69 (m, 1 H) 1.38-1.50 (m, 1 H) 1883-(pyridin-3-yl)- ¹H NMR (500 MHz DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))N-{4-[1- ppm 8.84 (s, 1 H) 8.74 (d, J = 5.19 Hz, 1 m/e 447 (thiophen-2-H) 8.51 (d, J = 7.93 Hz, 1 H) 7.95 (dd, J = 7.93, (M + H)⁺ylcarbonyl)piperidin- 5.49 Hz, 1 H) 7.69-7.80 (m, 1 H) 4- 7.39-7.46 (m,3 H) 7.10-7.19 (m, 3 H) 4.19-4.57 (m, 4 yl]phenyl}azetidine- H)3.99-4.13 (m, 3 H) 2.92-3.38 (m, 2 H) 1- 2.71-2.86 (m, 1 H) 1.83 (d, J =12.82 Hz, 2 H) carboxamide 1.48-1.65 (m, 2 H) 189 N-(4-{1-[(5- ¹H NMR(500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) methylthiophen- ppm 8.88(s, 1 H) 8.77 (d, J = 5.19 Hz, 1 m/e 461 2- H) 8.58 (d, J = 8.24 Hz, 1H) 8.01 (dd, J = 8.09, (M + H)⁺ yl)carbonyl]piperidin- 5.65 Hz, 1 H)7.42 (d, J = 8.54 Hz, 2 H) 7.23 (d, 4- J = 3.66 Hz, 1 H) 7.16 (d, J =8.54 Hz, 2 H) yl}phenyl)-3- 6.83 (d, J = 2.75 Hz, 1 H) 4.42 (t, J = 8.09Hz, 4 H) (pyridin-3- 3.98-4.16 (m, 3 H) 2.97-3.16 (m, 2 H)yl)azetidine-1- 2.71-2.85 (m, 1 H) 2.47 (s, 3 H) 1.82 (d, J = 12.51 Hz,carboxamide 2 H) 1.47-1.63 (m, 2 H) 190 N-{4-[1-(furan-2- ¹H NMR (500MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) ylcarbonyl)piperidin- ppm 8.87(s, 1 H) 8.77 (d, J = 5.49 Hz, 1 m/e 431 4-yl]phenyl}- H) 8.58 (d, J =8.24 Hz, 1 H) 8.00 (dd, J = 7.93, (M + H)⁺ 3-(pyridin-3- 5.49 Hz, 1 H)7.81 (s, 1 H) 7.42 (d, J = 8.54 Hz, yl)azetidine-1- 2 H) 7.11-7.21 (m, 2H) 6.99 (d, J = 3.66 Hz, 1 carboxamide H) 6.63 (dd, J = 3.51, 1.68 Hz, 1H) 4.42 (t, J = 8.09 Hz, 4 H) 3.99-4.15 (m, 3 H) 2.84-3.35 (m, 2 H)2.74-2.83 (m, 1 H) 1.85 (d, J = 12.51 Hz, 2 H) 1.56 (d, J = 10.07 Hz, 2H) 191 N-(4-{1-[(1- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))methyl-1H- ppm 8.87 (s, 1 H) 8.76 (d, J = 5.19 Hz, 1 m/e 444 pyrrol-2-H) 8.56 (d, J = 8.24 Hz, 1 H) 7.99 (dd, J = 7.93, (M + H)⁺yl)carbonyl]piperidin- 5.80 Hz, 1 H) 7.42 (d, J = 8.54 Hz, 2 H) 7.16 (d,4- J = 8.85 Hz, 2 H) 6.88 (d, J = 1.83 Hz, 1 H) yl}phenyl)-3- 6.33 (dd,J = 3.66, 1.53 Hz, 1 H) 6.01-6.06 (m, 1 H) (pyridin-3- 4.33-4.48 (m, J =8.09, 8.09 Hz, 4 H) yl)azetidine-1- 4.01-4.10 (m, 3 H) 3.66-3.67 (m, 3H) carboxamide 2.96-3.08 (m, 2 H) 2.71-2.82 (m, 1 H) 1.81 (d, J = 12.21Hz, 2 H) 1.47-1.61 (m, 2 H) 192 N-[4-(1- ¹H NMR (500 MHz, DMSO-d₆/D₂OTemp = 25° C.) (ESI(+)) propanoylpiperidin- ppm 8.89 (s, 1 H) 8.78 (d, J= 5.49 Hz, 1 m/e 393 4-yl)phenyl]-3- H) 8.53-8.65 (m, 1 H) 8.03 (dd, J =8.09, 5.65 Hz, (M + H)⁺ (pyridin-3- 1 H) 7.31-7.47 (m, 2 H) 7.08-7.17(m, 2 yl)azetidine-1- H) 4.52 (d, J = 12.51 Hz, 1 H) 4.42 (t, J = 8.24Hz, carboxamide 2 H) 3.92-4.16 (m, 4 H) 3.08 (t, J = 12.05 Hz, 1 H)2.57-2.76 (m, 2 H) 2.35 (q, J = 7.53 Hz, 2 H) 1.77 (t, J = 15.26 Hz, 2H)1.29-1.58 (m, 2 H) 1.01 (t, J = 7.48 Hz, 3 H) 193 N-(4-{1-[(1- ¹H NMR(500 MHz, DMSO-d₆/D₂O Temp = 25° C.) (ESI(+))methylcyclopropyl)carbonyl]piperidin- ppm 8.89 (s, 1 H) 8.78 (d, J =5.19 Hz, 1 m/e 419 4- H) 8.60 (t, J = 7.93 Hz, 1 H) 8.03 (dd, J = 7.93,(M + H)⁺ yl}phenyl)-3- 5.80 Hz, 1 H) 7.41 (d, J = 8.54 Hz, 2 H) 7.14 (d,(pyridin-3- J = 8.54 Hz, 2 H) 4.30-4.49 (m, 4 H) yl)azetidine-1-3.99-4.18 (m, 3 H) 2.65-3.18 (m, 3 H) 1.79 (d, J = 12.51 Hz, carboxamide2 H) 1.33-1.57 (m, 2 H) 1.25 (s, 3 H) 0.78-0.88 (m, 2 H) 0.50-0.60 (m, 2H) 194 3-(pyridin-3-yl)- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.)(ESI(+)) N-{4-[1- ppm 8.83 (s, 1 H) 8.73 (d, J = 5.19 Hz, 1 m/e 448(pyrrolidin-1- H) 8.47 (d, J = 8.24 Hz, 1 H) 7.93 (dd, J = 7.93, (M +H)⁺ ylacetyl)piperidin- 5.80 Hz, 1 H) 7.42 (d, J = 8.54 Hz, 2 H) 7.13(d, 4- J = 8.54 Hz, 2 H) 4.26-4.52 (m, 5 H) yl]phenyl}azetidine-3.97-4.10 (m, 3 H) 3.64-3.67 (m, 1 H) 3.59 (d, J = 6.41 Hz, 1- 2 H)2.96-3.24 (m, 3 H) 2.76 (t, J = 12.36 Hz, carboxamide 2 H) 1.77-2.09 (m,6 H) 1.36-1.66 (m, 2 H) 195 3-(pyridin-3-yl)- ¹H NMR (500 MHz,DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) N-{4-[1-(1,3- ppm 8.86 (s, 1 H) 8.76(d, J = 5.49 Hz, 1 m/e 448 thiazol-2- H) 8.55 (d, J = 8.24 Hz, 1 H)7.94-8.04 (m, 3 H) (M + H)⁺ ylcarbonyl)piperidin- 7.42 (d, J = 8.54 Hz,2 H) 7.16 (d, J = 8.85 Hz, 2 4- H) 5.35 (d, J = 12.82 Hz, 1 H) 4.61 (d,J = 11.90 Hz, yl]phenyl}azetidine- 1 H) 4.42 (t, J = 7.93 Hz, 2 H) 1-3.99-4.10 (m, 3 H) 3.27 (t, J = 12.66 Hz, 1 H) carboxamide 2.78-2.99 (m,2 H) 1.80-1.91 (m, 2 H) 1.52-1.69 (m, 2 H) 196 N-{4-[1- ¹H NMR (500 MHz,DMSO-d₆/D₂O Temp = 25° C.) (ESI(+)) (cyclopentylacetyl)piperidin- ppm8.88 (s, 1 H) 8.77 (d, J = 5.49 Hz, 1 m/e 447 4- H) 8.59 (d, J = 8.24Hz, 1 H) 8.01 (dd, J = 8.09, (M + H)⁺ yl]phenyl}-3- 5.65 Hz, 1 H) 7.41(d, J = 8.54 Hz, 2 H) 7.12 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.53 (d, J= 13.12 Hz, 1 H) yl)azetidine-1- 4.42 (t, J = 8.09 Hz, 2 H) 3.92-4.14(m, 4 H) 3.09 (t, carboxamide J = 12.05 Hz, 1 H) 2.55-2.79 (m, 2 H) 2.36(d, J = 7.32 Hz, 2 H) 2.04-2.22 (m, 1 H) 1.30-1.90 (m, 10 H) 1.05-1.20(m, 2 H) 197 N-{4-[1-(2,3- ¹H NMR (500 MHz, DMSO-d₆/D₂O Temp = 25° C.)(ESI(+)) dimethylbutanoyl)piperidin- ppm 8.87 (s, 1 H) 8.76 (d, J = 5.19Hz, 1 m/e 435 4- H) 8.56 (d, J = 8.24 Hz, 1 H) 7.99 (dd, J = 7.93, (M +H)⁺ yl]phenyl}-3- 5.80 Hz, 1 H) 7.38-7.45 (m, 2 H) (pyridin-3- 7.06-7.16(m, 2 H) 4.54-4.63 (m, 1 H) 4.42 (t, J = 8.09 Hz, yl)azetidine-1- 2 H)3.99-4.18 (m, 4 H) 3.11 (t, J = 12.21 Hz, 1 carboxamide H) 2.69-2.80 (m,1 H) 2.54-2.63 (m, 2 H) 1.70-1.93 (m, 3 H) 1.29-1.56 (m, 2 H) 0.93-1.07(m, 3 H) 0.78-0.90 (m, 6 H) 198 N-[4-(1- ¹H NMR (400 MHz, DMSO-d₆/D₂OTemp = 90° C.) (ESI(+)) pentanoylazetidin- ppm 8.71 (d, J = 2.14 Hz, 1H) m/e 393 3-yl)phenyl]-3- 8.60-8.65 (m, 1 H) 8.24 (d, J = 7.93 Hz, 1 H)7.75 (dd, (M + H)⁺ (pyridin-3- J = 8.09, 5.34 Hz, 1 H) 7.47 (d, J = 8.54Hz, 2 H) yl)azetidine-1- 7.21 (d, J = 8.54 Hz, 2 H) 4.31-4.53 (m, 4 H)carboxamide 3.97-4.09 (m, 4 H) 3.71-3.85 (m, 2 H) 2.08 (t, J = 7.32 Hz,2 H) 1.45-1.57 (m, 2 H) 1.25-1.37 (m, 2 H) 0.88 (t, J = 7.32 Hz, 3 H)199 N-(4-{1-[(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))methylcyclopropyl)carbonyl]azetidin- ppm 8.71 (d, J = 1.83 Hz, 1 H) 8.62(d, m/e 391 3-yl}phenyl)- J = 5.19 Hz, 1 H) 8.23 (d, J = 8.24 Hz, 1 H)(M + H)⁺ 3-(pyridin-3- 7.74 (dd, J = 7.93, 5.49 Hz, 1 H) 7.48 (d, J =8.54 Hz, 2 yl)azetidine-1- H) 7.19-7.25 (m, 2 H) 4.36-4.50 (m, 4 H)carboxamide 3.92-4.11 (m, 4 H) 3.76-3.89 (m, 2 H) 1.25-1.33 (m, 1 H)1.12-1.20 (m, 1 H) 1.04-1.10 (m, 3 H) 0.88-0.98 (m, 1 H) 0.53-0.63 (m, 1H) 200 N-(4-{1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))[(1S,4R)- ppm 8.71 (d, J = 1.83 Hz, 1 H) m/e 445 bicyclo[2.2.1]hept-8.59-8.66 (m, 1 H) 8.24 (d, J = 7.93 Hz, 1 H) 7.74 (dd, (M + H)⁺ 2- J =7.93, 5.19 Hz, 1 H) 7.42-7.51 (m, 2 H) ylacetyl]azetidin- 7.20 (d, J =8.85 Hz, 2 H) 4.31-4.61 (m, 4 H) 3-yl}phenyl)-3- 3.92-4.13 (m, 4 H)3.66-3.82 (m, 2 H) 2.17 (s, 1 H) (pyridin-3- 2.01-2.11 (m, 1 H)1.88-2.00 (m, 2 H) yl)azetidine-1- 1.75-1.86 (m, 1 H) 1.37-1.52 (m, 3 H)carboxamide 1.29-1.35 (m, 1 H) 1.00-1.22 (m, 4 H) 201 N-{4-[1-(4- ¹H NMR(400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) methylpentanoyl)azetidin-ppm 8.72 (d, J = 1.83 Hz, 1 H) 8.63 (dd, m/e 407 3- J = 5.34, 1.37 Hz, 1H) 8.27 (d, J = 8.24 Hz, 1 H) (M + H)⁺ yl]phenyl}-3- 7.77 (dd, J = 7.93,5.19 Hz, 1 H) 7.47 (d, J = 8.54 Hz, (pyridin-3- 2 H) 7.21 (d, J = 8.54Hz, 2 H) yl)azetidine-1- 4.25-4.58 (m, 4 H) 3.96-4.13 (m, 4 H) 3.72-3.86(m, 2 carboxamide H) 2.05-2.11 (m, 2 H) 1.49-1.66 (m, 1 H) 1.38-1.46 (m,2 H) 0.88 (d, J = 6.71 Hz, 6 H) 202 N-{4-[1-(3- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) methylpentanoyl)azetidin- ppm 8.71(d, J = 1.83 Hz, 1 H) m/e 407 3- 8.58-8.64 (m, 1 H) 8.25 (d, J = 7.93Hz, 1 H) 7.76 (dd, (M + H)⁺ yl]phenyl}-3- J = 7.93, 5.19 Hz, 1 H) 7.47(d, J = 8.54 Hz, 2 H) (pyridin-3- 7.20 (d, J = 8.54 Hz, 2 H) 4.29-4.64(m, 4 H) yl)azetidine-1- 3.95-4.18 (m, 4 H) 3.68-3.88 (m, 2 H)carboxamide 1.99-2.14 (m, 1 H) 1.87-1.96 (m, 1 H) 1.73-1.86 (m, 1 H)1.29-1.46 (m, 1 H) 1.14-1.27 (m, 1 H) 0.83-0.92 (m, 6 H) 203 N-{4-[1-(3-¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))ethoxypropanoyl)azetidin- ppm 8.70 (d, J = 1.83 Hz, 1 H) m/e 409 3-8.57-8.65 (m, 1 H) 8.22 (d, J = 8.24 Hz, 1 H) 7.73 (dd, (M + H)⁺yl]phenyl}-3- J = 7.93, 5.19 Hz, 1 H) 7.47 (d, J = 8.54 Hz, 2 H)(pyridin-3- 7.21 (d, J = 8.54 Hz, 2 H) 4.28-4.62 (m, 4 H)yl)azetidine-1- 3.93-4.22 (m, 4 H) 3.70-3.83 (m, 2 H) 3.61 (t,carboxamide J = 6.41 Hz, 2 H) 3.44 (q, J = 7.02 Hz, 2 H) 2.28-2.38 (m, 2H) 1.11 (t, J = 6.87 Hz, 3 H) 204 N-{4-[1-(2,2- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) dimethylbutanoyl)azetidin- ppm 8.71(d, J = 2.14 Hz, 1 H) 8.63 (dd, m/e 407 3- J = 5.34, 1.37 Hz, 1 H) 8.25(d, J = 8.24 Hz, 1 H) (M + H)⁺ yl]phenyl}-3- 7.76 (dd, J = 7.93, 5.49Hz, 1 H) 7.47 (d, J = 8.54 Hz, (pyridin-3- 2 H) 7.20 (d, J = 8.54 Hz, 2H) yl)azetidine-1- 4.33-4.64 (m, 4 H) 3.93-4.12 (m, 5 H) 3.70-3.81 (m, 1carboxamide H) 1.51 (q, J = 7.32 Hz, 2 H) 1.11 (s, 6 H) 0.83 (t, J =7.48 Hz, 3 H);) 205 N-{4-[1-(3,3- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp =90° C.) (ESI(+)) dimethylbutanoyl)azetidin- ppm 8.72 (d, J = 1.83 Hz, 1H) 8.63 (dd, m/e 407 3- J = 5.49, 1.22 Hz, 1 H) 8.26 (d, J = 8.24 Hz, 1H) (M + H)⁺ yl]phenyl}-3- 7.76 (dd, J = 7.93, 5.19 Hz, 1 H) 7.47 (d, J =8.54 Hz, (pyridin-3- 2 H) 7.20 (d, J = 8.54 Hz, 2 H) yl)azetidine-1-4.19-4.62 (m, 4 H) 3.90-4.05 (m, 4 H) 3.59-3.85 (m, 2 carboxamide H)1.98 (s, 2 H) 1.01 (s, 9 H) 206 N-{4-[1-(2,2- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) dimethylpropanoyl)azetidin- ppm 8.73(d, J = 1.83 Hz, 1 H) 8.64 (d, m/e 393 3- J = 5.49 Hz, 1 H) 8.28 (d, J =7.93 Hz, 1 H) (M + H)⁺ yl]phenyl}-3- 7.78 (dd, J = 8.09, 5.34 Hz, 1 H)7.47 (d, J = 8.54 Hz, 2 (pyridin-3- H) 7.20 (d, J = 8.54 Hz, 2 H)4.36-4.57 (m, 4 H) yl)azetidine-1- 3.93-4.14 (m, 5 H) 3.67-3.84 (m, 1 H)1.15 (s, carboxamide 9 H) 207 N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp= 90° C.) (ESI(+)) (ethoxyacetyl)azetidin- ppm 8.72 (d, J = 1.83 Hz, 1H) 8.63 (d, m/e 395 3- J = 5.19 Hz, 1 H) 8.26 (d, J = 7.93 Hz, 1 H) (M +H)⁺ yl]phenyl}-3- 7.76 (dd, J = 7.93, 5.19 Hz, 1 H) 7.44-7.51 (m, 2 H)(pyridin-3- 7.17-7.25 (m, J = 8.09, 8.09 Hz, 2 H) yl)azetidine-1-4.21-4.64 (m, 4 H) 3.97-4.18 (m, 5 H) 3.95 (s, 2 H) carboxamide3.78-3.87 (m, 1 H) 3.50 (q, J = 6.92 Hz, 2 H) 1.10-1.18 (m, 3 H) 208N-{4-[1-(3- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))methylbutanoyl)azetidine- ppm 8.72 (d, J = 1.83 Hz, 1 H) m/e 393 3-8.61-8.65 (m, 1 H) 8.28 (d, J = 8.24 Hz, 1 H) 7.77 (dd, (M + H)⁺yl]phenyl}-3- J = 7.93, 5.49 Hz, 1 H) 7.47 (d, J = 8.54 Hz, 2 H)(pyridin-3- 7.20 (d, J = 8.54 Hz, 2 H) 4.23-4.59 (m, 4 H)yl)azetidine-1- 3.95-4.24 (m, 4 H) 3.71-3.83 (m, 2 H) carboxamide1.92-2.05 (m, 3 H) 0.92 (d, J = 6.10 Hz, 6 H) 209 N-{4-[1-(N- ¹H NMR(400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) acetyl-L- ppm 8.73 (d, J =2.14 Hz, 1 H) m/e 464 leucyl)azetidin-3- 8.62-8.65 (m, 1 H) 8.28 (d, J =8.24 Hz, 1 H) (M + H)⁺ yl]phenyl}-3- 7.73-7.79 (m, 1 H) 7.47 (d, J =8.54 Hz, 2 H) 7.21 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.20-4.87 (m, 4 H)yl)azetidine-1- 3.91-4.21 (m, 4 H) 3.65-3.92 (m, 2 H) 1.84-1.88 (m, 3carboxamide H) 1.55-1.71 (m, 1 H) 1.42-1.55 (m, 2 H) 0.82-0.97 (m, 7 H)210 N-(4-{1-[(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))methoxyethoxy)acetyl]azetidin- ppm 8.71 (d, J = 1.83 Hz, 1 H) 8.62 (dd,m/e 425 3- J = 5.19, 1.22 Hz, 1 H) 8.24 (d, J = 7.93 Hz, 1 H) (M + H)⁺yl}phenyl)-3- 7.74 (dd, J = 7.93, 5.19 Hz, 1 H) 7.47 (d, J = 8.54 Hz,(pyridin-3- 2 H) 7.22 (d, J = 8.54 Hz, 2 H) yl)azetidine-1- 4.20-4.80(m, 5 H) 3.91-4.14 (m, 8 H) 3.75-3.91 (m, 2 carboxamide H) 3.56-3.61 (m,2 H) 3.45-3.51 (m, 2 H) 211 N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp =90° C.) (ESI(+)) (cyclohexylcarbonyl)azetidin- ppm 8.72 (d, J = 1.53 Hz,1 H) 8.63 (d, m/e 419 3- J = 4.27 Hz, 1 H) 8.26 (d, J = 7.93 Hz, 1 H)(M + H)⁺ yl]phenyl}-3- 7.73-7.77 (m, 1 H) 7.47 (d, J = 8.54 Hz, 2 H)7.20 (d, (pyridin-3- J = 8.54 Hz, 2 H) 4.18-4.63 (m, 4 H)yl)azetidine-1- 3.90-4.15 (m, 4 H) 3.67-3.87 (m, 2 H) 2.15-2.31 (m, 1carboxamide H) 1.53-1.88 (m, 5 H) 1.08-1.46 (m, 5 H) 212 N-{4-[1- ¹H NMR(400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))(cyclohexylacetyl)azetidin- ppm 8.74 (d, J = 1.83 Hz, 1 H) m/e 433 3-8.61-8.68 (m, 1 H) 8.31 (d, J = 8.24 Hz, 1 H) 7.80 (dd, (M + H)⁺yl]phenyl}-3- J = 7.93, 5.19 Hz, 1 H) 7.47 (d, J = 8.54 Hz, 2 H)(pyridin-3- 7.20 (d, J = 8.54 Hz, 2 H) 4.21-4.72 (m, 4 H)yl)azetidine-1- 3.87-4.20 (m, 4 H) 3.62-3.84 (m, 2 H) carboxamide 1.97(d, J = 6.41 Hz, 2 H) 1.52-1.79 (m, 6 H) 1.07-1.33 (m, 3 H) 0.91-1.06(m, 2 H) 213 3-(pyridin-3-yl)- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90°C.) (ESI(+)) N-{4-[1-(4,4,4- ppm 8.72 (d, J = 1.83 Hz, 1 H) 8.63 (d, m/e433 trifluorobutanoyl)azetidin- J = 4.27 Hz, 1 H) 8.26 (d, J = 7.93 Hz,1 H) (M + H)⁺ 3- 7.76 (dd, J = 7.93, 5.19 Hz, 1 H) 7.47 (d, J = 8.54 Hz,2 yl]phenyl}azetidine- H) 7.22 (d, J = 8.54 Hz, 2 H) 4.18-4.81 (m, 4 H)1- 3.96-4.16 (m, 4 H) 3.73-3.89 (m, 2 H) carboxamide 2.42-2.50 (m, 2 H)2.32-2.40 (m, 2 H) 214 N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90°C.) (ESI(+)) (cyclopentylcarbonyl)azetidin- ppm 8.74 (d, J = 1.83 Hz, 1H) 8.65 (d, m/e 405 3- J = 5.49 Hz, 1 H) 8.31 (d, J = 7.93 Hz, 1 H) (M +H)⁺ yl]phenyl}-3- 7.80 (dd, J = 7.93, 5.49 Hz, 1 H) 7.47 (d, J = 8.54Hz, 2 (pyridin-3- H) 7.21 (d, J = 8.54 Hz, 2 H) 4.12-4.74 (m, 4 H)yl)azetidine-1- 3.85-4.23 (m, 4 H) 3.71-3.86 (m, 2 H) carboxamide 2.73(m, 1 H) 1.38-1.87 (m, 8 H) 215 N-(4-{1-[(1- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) methylcyclohexyl)carbonyl]azetidin-ppm 8.73 (d, J = 1.83 Hz, 1 H) 8.64 (d, m/e 433 3-yl}phenyl)-3- J = 5.19Hz, 1 H) 8.28 (d, J = 7.93 Hz, 1 H) (M + H)⁺ (pyridin-3- 7.78 (dd, J =8.09, 5.34 Hz, 1 H) 7.47 (d, J = 8.54 Hz, 2 yl)azetidine-1- H) 7.20 (d,J = 8.54 Hz, 2 H) 4.35-4.68 (m, 4 H) carboxamide 3.89-4.13 (m, 5 H)3.70-3.80 (m, 1 H) 1.88-1.99 (m, 2 H) 1.15-1.66 (m, 8 H) 1.11 (s, 3 H)216 N-{4-[1-(furan-3- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.)(ESI(+)) ylcarbonyl)azetidin- ppm 8.72 (d, J = 2.14 Hz, 1 H) m/e 4033-yl]phenyl}- 8.62-8.66 (m, 1 H) 8.27 (d, J = 7.94 Hz, 1 H) 8.06 (s, 1H) (M + H)⁺ 3-(pyridin-3- 7.77 (dd, J = 7.93, 5.49 Hz, 1 H) 7.65-7.68(m, yl)azetidine-1- 1 H) 7.48 (d, J = 8.54 Hz, 2 H) 7.25 (d, J = 8.85Hz, carboxamide 2 H) 6.73 (d, J = 1.83 Hz, 1 H) 4.32-4.84 (m, 4 H)3.96-4.25 (m, 5 H) 3.84-3.93 (m, 1 H) 217 N-[4-(1- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) acetylazetidin-3- ppm 8.73 (d, J =1.83 Hz, 1 H) m/e 351 yl)phenyl]-3- 8.60-8.67 (m, 1 H) 8.29 (d, J = 7.93Hz, 1 H) 7.78 (dd, (M + H)⁺ (pyridin-3- J = 7.93, 5.49 Hz, 1 H) 7.47 (d,J = 8.54 Hz, 2 H) yl)azetidine-1- 7.22 (d, J = 8.54 Hz, 2 H) 4.13-4.65(m, 4 H) carboxamide 3.89-4.21 (m, 4 H) 3.67-3.90 (m, 2 H) 1.80 (s, 3 H)218 N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))(methoxyacetyl)azetidin- ppm 8.72 (d, J = 2.14 Hz, 1 H) 8.63 (dd, m/e381 3- J = 5.19, 1.22 Hz, 1 H) 8.26 (d, J = 8.24 Hz, 1 H) (M + H)⁺yl]phenyl}-3- 7.76 (dd, J = 7.93, 5.19 Hz, 1 H) 7.47 (d, J = 8.54 Hz,(pyridin-3- 2 H) 7.22 (d, J = 8.54 Hz, 2 H) yl)azetidine-1- 4.33-4.52(m, 4 H) 3.96-4.11 (m, 5 H) 3.92 (s, 2 H) carboxamide 3.80-3.89 (m, 1 H)3.31 (s, 3 H) 219 3-(pyridin-3-yl)- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp =90° C.) (ESI(+)) N-{4-[1- ppm 8.73 (d, J = 1.83 Hz, 1 H) 8.64 (dd, m/e419 (thiophen-3- J = 5.19, 1.22 Hz, 1 H) 8.28 (d, J = 7.93 Hz, 1 H) (M +H)⁺ ylcarbonyl)azetidin- 7.97 (dd, J = 3.05, 1.22 Hz, 1 H) 7.78 (dd, 3-J = 8.09, 5.34 Hz, 1 H) 7.54 (dd, J = 5.04, 2.90 Hz,yl]phenyl}azetidine- 1 H) 7.48 (d, J = 8.54 Hz, 2 H) 7.39 (dd, 1- J =4.88, 1.22 Hz, 1 H) 7.25 (d, J = 8.54 Hz, 2 H) carboxamide 4.38-4.76 (m,4 H) 3.99-4.25 (m, 5 H) 3.85-3.94 (m, 1 H) 220 N-(4-{1-[(3- ¹H NMR (400MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) methylthiophen- ppm 8.73 (d, J= 2.14 Hz, 1 H) 8.64 (dd, m/e 433 2- J = 5.49, 1.22 Hz, 1 H) 8.29 (d, J= 7.94 Hz, 1 H) (M + H)⁺ yl)carbonyl]azetidin- 7.78 (dd, J = 8.09, 5.34Hz, 1 H) 7.56 (d, J = 5.19 Hz, 3-yl}phenyl)- 1 H) 7.48 (d, J = 8.54 Hz,2 H) 7.23 (d, 3-(pyridin-3- J = 8.54 Hz, 2 H) 6.98 (d, J = 4.88 Hz, 1 H)yl)azetidine-1- 4.53 (t, J = 9.00 Hz, 2 H) 4.38-4.48 (m, 2 H)carboxamide 3.96-4.16 (m, 5 H) 3.81-3.92 (m, 1 H) 2.41 (s, 3 H) 221N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))(morpholin-4- ppm 8.68 (d, J = 1.83 Hz, 1 H) 8.60 (dd, m/e 436ylacetyl)azetidin- J = 5.19, 1.22 Hz, 1 H) 8.15 (d, J = 7.93 Hz, 1 H)(M + H)⁺ 3-yl]phenyl}-3- 7.68 (dd, J = 7.93, 5.19 Hz, 1 H) 7.49 (d, J =8.54 Hz, (pyridin-3- 2 H) 7.24 (d, J = 8.54 Hz, 2 H) yl)azetidine-1-4.27-5.16 (m, 4 H) 3.95-4.29 (m, 7 H) 3.81-3.95 (m, 5 carboxamide H)3.30-3.36 (m, 4 H) 222 3-(pyridin-3-yl)- ¹H NMR (400 MHz, DMSO-d₆/D₂OTemp = 90° C.) (ESI(+)) N-{4-[1- ppm 8.72 (d, J = 1.83 Hz, 1 H) m/e 419(thiophen-2- 8.61-8.65 (m, 1 H) 8.27 (d, J = 7.93 Hz, 1 H) (M + H)⁺ylcarbonyl)azetidin- 7.71-7.80 (m, 2 H) 7.54 (d, J = 2.75 Hz, 1 H) 7.49(d, 3- J = 8.54 Hz, 2 H) 7.26 (d, J = 8.54 Hz, 2 H) yl]phenyl}azetidine-7.16 (dd, J = 4.88, 3.66 Hz, 1 H) 4.65 (s, 2 H) 1- 4.39-4.49 (m, 2 H)4.21 (s, 2 H) 3.97-4.09 (m, 3 H) carboxamide 3.87-3.96 (m, 1 H) 223N-(4-{1-[(5- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))methylthiophen- ppm 8.71 (d, J = 1.83 Hz, 1 H) 8.63 (d, m/e 433 2- J =4.27 Hz, 1 H) 8.25 (d, J = 8.24 Hz, 1 H) (M + H)⁺ yl)carbonyl]azetidin-7.75 (dd, J = 7.93, 5.19 Hz, 1 H) 7.48 (d, J = 8.54 Hz, 2 3-yl}phenyl)-H) 7.34 (d, J = 3.66 Hz, 1 H) 7.25 (d, J = 8.54 Hz, 3-(pyridin-3- 2 H)6.85 (d, J = 3.66 Hz, 1 H) 4.62 (t, J = 8.39 Hz, yl)azetidine-1- 2 H)4.37-4.48 (m, 2 H) 4.18 (t, J = 6.41 Hz, carboxamide 2 H) 3.97-4.09 (m,3 H) 3.86-3.94 (m, 1 H) 2.47 (s, 3 H) 224 N-{4-[1-(furan-2- ¹H NMR (400MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) ylcarbonyl)azetidin- ppm 8.73(d, J = 2.14 Hz, 1 H) 8.64 (dd, m/e 403 3-yl]phenyl}- J = 5.19, 1.22 Hz,1 H) 8.28 (d, J = 7.93 Hz, 1 H) (M + H)⁺ 3-(pyridin-3- 7.70-7.82 (m, 2H) 7.48 (d, J = 8.54 Hz, 2 H) yl)azetidine-1- 7.25 (d, J = 8.54 Hz, 2 H)7.02 (d, J = 3.66 Hz, 1 carboxamide H) 6.60 (dd, J = 3.51, 1.68 Hz, 1 H)4.64 (s, 2 H) 4.34-4.52 (m, 2 H) 4.20 (s, 2 H) 3.98-4.10 (m, 3 H)3.86-3.97 (m, 1 H) 225 N-(4-{1-[(1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp =90° C.) (ESI(+)) methyl-1H- ppm 8.72 (d, J = 1.83 Hz, 1 H) 8.63 (d, m/e416 pyrrol-2- J = 5.19 Hz, 1 H) 8.26 (d, J = 7.93 Hz, 1 H) (M + H)⁺yl)carbonyl]azetidin- 7.76 (dd, J = 8.09, 5.34 Hz, 1 H) 7.48 (d, J =8.54 Hz, 2 3-yl}phenyl)- H) 7.24 (d, J = 8.54 Hz, 2 H) 6.88 (d, J = 2.14Hz, 3-(pyridin-3- 1 H) 6.52 (dd, J = 3.97, 1.53 Hz, 1 H) 6.06 (dd,yl)azetidine-1- J = 3.81, 2.59 Hz, 1 H) 4.54 (t, J = 8.85 Hz, 2 H)carboxamide 4.37-4.47 (m, 2 H) 4.10 (t, J = 9.00, 6.26 Hz, 2 H)3.98-4.06 (m, 3 H) 3.85-3.89 (m, 1 H) 3.84 (s, 3 H) 226 N-[4-(1- ¹H NMR(400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) propanoylazetidin- ppm8.72 (d, J = 1.83 Hz, 1 H) 8.64 (dd, m/e 365 3-yl)phenyl]-3- J = 5.19,1.22 Hz, 1 H) 8.28 (d, J = 8.24 Hz, 1 H) (M + H)⁺ (pyridin-3- 7.78 (dd,J = 7.93, 5.49 Hz, 1 H) 7.47 (d, J = 8.54 Hz, yl)azetidine-1- 2 H) 7.21(d, J = 8.54 Hz, 2 H) carboxamide 4.19-4.68 (m, 4 H) 3.90-4.14 (m, 4 H)3.70-3.87 (m, 2 H) 2.10 (q, J = 7.53 Hz, 2 H) 1.01 (t, J = 7.63 Hz, 3 H)227 N-(4-{1-[(1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))methylcyclopropyl)carbonyl]azetidin- ppm 8.73 (d, J = 2.14 Hz, 1 H) 8.64(d, m/e 391 3-yl}phenyl)- J = 5.19 Hz, 1 H) 8.29 (d, J = 7.93 Hz, 1 H)(M + H)⁺ 3-(pyridin-3- 7.75-7.80 (m, 1 H) 7.48 (d, J = 8.54 Hz, 2 H)7.21 (d, yl)azetidine-1- J = 8.54 Hz, 2 H) 4.37-4.52 (m, 4 H)carboxamide 3.97-4.12 (m, 5 H) 3.72-3.87 (m, 1 H) 1.27 (s, 3 H)0.88-0.97 (m, 2 H) 0.44-0.53 (m, 2 H) 228 3-(pyridin-3-yl)- ¹H NMR (400MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) N-{4-[1-(1,3- ppm 8.72 (d, J =1.83 Hz, 1 H) 8.63 (dd, m/e 420 thiazol-2- J = 5.34, 1.37 Hz, 1 H) 8.26(d, J = 8.24 Hz, 1 H) (M + H)⁺ ylcarbonyl)azetidin- 7.99 (d, J = 3.05Hz, 1 H) 7.91 (d, J = 3.05 Hz, 1 3- H) 7.76 (dd, J = 7.93, 5.19 Hz, 1 H)7.49 (d, yl]phenyl}azetidine- J = 8.54 Hz, 2 H) 7.24-7.30 (m, 2 H) 5.01(s, 1 1- H) 4.35-4.79 (m, 4 H) 3.86-4.24 (m, 5 H) carboxamide 229N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))(cyclopentylacetyl)azetidin- ppm 8.71 (d, J = 1.83 Hz, 1 H) 8.63 (dd,m/e 419 3- J = 5.49, 1.22 Hz, 1 H) 8.25 (d, J = 7.93 Hz, 1 H) (M + H)⁺yl]phenyl}-3- 7.75 (dd, J = 8.09, 5.34 Hz, 1 H) 7.47 (d, J = 8.54 Hz,(pyridin-3- 2 H) 7.20 (d, J = 8.54 Hz, 2 H) yl)azetidine-1- 4.14-4.78(m, 4 H) 3.82-4.18 (m, 4 H) 3.62-3.86 (m, 2 carboxamide H) 2.05-2.22 (m,3 H) 1.68-1.83 (m, 2 H) 1.40-1.65 (m, 4 H) 1.09-1.21 (m, 2 H) 230N-{4-[1-(2,3- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))dimethylbutanoyl)azetidin- ppm 8.73 (d, J = 1.83 Hz, 1 H) m/e 407 3-8.62-8.67 (m, 1 H) 8.30 (d, J = 8.24 Hz, 1 H) 7.80 (dd, (M + H)⁺yl]phenyl}-3- J = 7.93, 5.19 Hz, 1 H) 7.47 (d, J = 8.54 Hz, 2 H)(pyridin-3- 7.20 (d, J = 8.54 Hz, 2 H) 4.16-4.68 (m, 4 H)yl)azetidine-1- 3.90-4.26 (m, 5 H) 3.66-3.89 (m, 1 H) carboxamide2.01-2.19 (m, 1 H) 1.65-1.85 (m, 1 H) 0.98 (d, J = 6.71 Hz, 3 H) 0.89(dd, J = 6.56, 4.12 Hz, 6 H) 258 N-[4-(1- (ESI(+)) pentanoylpyrrolidin-m/e 407 3-yl)phenyl]- (M + H)⁺ 3-(pyridin-3- yl)azetidine-1- carboxamide259 N-{4-[1-(3- (ESI(+)) methylpentanoyl)pyrrolidin- m/e 421 3- (M + H)⁺yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 260 N-(4-{1-(ESI(+)) [(1S,4R)- m/e 459 bicyclo[2.2.1]hept- (M + H)⁺ 2-ylacetyl]pyrrolidin- 3-yl}phenyl)-3- (pyridin-3- yl)azetidine-1-carboxamide 261 N-{4-[1- (ESI(+)) (cyclopentylacetyl)pyrrolidin- m/e 4333- (M + H)⁺ yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 262N-(4-{1-[(2- (ESI(+)) methylcyclopropyl)carbonyl]pyrrolidin- m/e 405 3-(M + H)⁺ yl}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 263N-{4-[1- (ESI(+)) (morpholin-4- m/e 450 ylacetyl)pyrrolidin- (M + H)⁺3-yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 264N-{4-[1-(furan-3- (ESI(+)) ylcarbonyl)pyrrolidin- m/e 417 3- (M + H)⁺yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 2653-(pyridin-3-yl)- (ESI(+)) N-{4-[1- m/e 434 (pyrrolidin-1- (M + H)⁺ylacetyl)pyrrolidin- 3- yl]phenyl}azetidine- 1- carboxamide 266N-{4-[1-(N,N- (ESI(+)) dimethyl-beta- m/e 422 alanyl)pyrrolidin- (M +H)⁺ 3-yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 2673-(pyridin-3-yl)- (ESI(+)) N-{4-[1-(1,3- m/e 434 thiazol-2- (M + H)⁺ylcarbonyl)pyrrolidin-3- yl]phenyl}azetidine- 1- carboxamide 2683-(pyridin-3-yl)- (ESI(+)) N-{4-[1- m/e 433 (thiophen-3- (M + H)⁺ylcarbonyl)pyrrolidin- 3- yl]phenyl}azetidine- 1- carboxamide 269N-(4-{1-[(1- (ESI(+)) methylcyclopropyl)carbonyl]pyrrolidin- m/e 405 3-(M + H)⁺ yl}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 270N-(4-{1-[(3- (ESI(+)) methylthiophen- m/e 447 2- (M + H)⁺yl)carbonyl]pyrrolidin- 3- yl}phenyl)-3- (pyridin-3- yl)azetidine-1-carboxamide 271 3-(pyridin-3-yl)- (ESI(+)) N-{4-[1-(4,4,4- m/e 447trifluorobutanoyl)pyrrolidin- (M + H)⁺ 3- yl]phenyl}azetidine- 1-carboxamide 272 N-(4-{1-[(4- (ESI(+)) methylpiperazin- m/e 463 1- (M +H)⁺ yl)acetyl]pyrrolidin- 3-yl}phenyl)- 3-(pyridin-3- yl)azetidine-1-carboxamide 273 N-{4-[1-(5-oxo- (ESI(+)) L- m/e 434 prolyl)pyrrolidin-(M + H)⁺ 3-yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 274N-{4-[1-(3- (ESI(+)) ethoxypropanoyl) m/e 423 pyrrolidin-3- (M + H)⁺yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 275 N-{4-[1-(4-(ESI(+)) methylpentanoyl)pyrrolidin- m/e 421 3- (M + H)⁺ yl]phenyl}-3-(pyridin-3- yl)azetidine-1- carboxamide 276 N-(4-{1-[(1- (ESI(+))methylcyclohexyl)carbonyl]pyrrolidin- m/e 447 3-yl}phenyl)- (M + H)⁺3-(pyridin-3- yl)azetidine-1- carboxamide 277 N-[4-(1- (ESI(+))acetylpyrrolidin- m/e 365 3-yl)phenyl]-3- (M + H)⁺ (pyridin-3-yl)azetidine-1- carboxamide 278 N-{4-[1- (ESI(+))(cyclohexylacetyl)pyrrolidin- m/e 447 3- (M + H)⁺ yl]phenyl}-3-(pyridin-3- yl)azetidine-1- carboxamide 279 N-[4-(1- (ESI(+))propanoylpyrrolidin- m/e 379 3-yl)phenyl]- (M + H)⁺ 3-(pyridin-3-yl)azetidine-1- carboxamide 280 N-(4-{1-[(2- (ESI(+))methoxyethoxy)acetyl]pyrrolidin- m/e 439 3-yl}phenyl)-3- (M + H)⁺(pyridin-3- yl)azetidine-1- carboxamide 281 N-(4-{1-[3- (ESI(+))(morpholin-4- m/e 464 yl)propanoyl]pyrrolidin- (M + H)⁺ 3- yl}phenyl)-3-(pyridin-3- yl)azetidine-1- carboxamide 282 N-{4-[1-(2,2- (ESI(+))dimethylpropanoyl)pyrrolidin- m/e 407 3- (M + H)⁺ yl]phenyl}-3-(pyridin-3- yl)azetidine-1- carboxamide 283 N-(4-{1-[(5- (ESI(+))methylthiophen- m/e 447 2- (M + H)⁺ yl)carbonyl]pyrrolidin- 3-yl}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 2843-(pyridin-3-yl)- (ESI(+)) N-{4-[1- m/e 433 (thiophen-2- (M + H)⁺ylcarbonyl)pyrrolidin-3- yl]phenyl}azetidine- 1- carboxamide 285N-(4-{1-[(1- (ESI(+)) methyl-1H- m/e 430 pyrrol-2- (M + H)⁺yl)carbonyl]pyrrolidin- 3- yl}phenyl)-3- (pyridin-3- yl)azetidine-1-carboxamide 286 N-{4-[1-(furan-2- (ESI(+)) ylcarbonyl)pyrrolidin- m/e417 3- (M + H)⁺ yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide287 N-(4-{1-[3- (ESI(+)) (piperidin-1- m/e 462 yl)propanoyl]pyrrolidin-(M + H)⁺ 3- yl}phenyl)-3- (pyridin-3- yl)azetidine-1- carboxamide 288N-{4-[1- (ESI(+)) (ethoxyacetyl)pyrrolidin- m/e 409 3- (M + H)⁺yl]phenyl}-3- (pyridin-3- yl)azetidine-1- carboxamide 289 N-{4-[1-(3,3-(ESI(+)) dimethylbutanoyl)pyrrolidin- m/e 421 3- (M + H)⁺ yl]phenyl}-3-(pyridin-3- yl)azetidine-1- carboxamide 290 N-{4-[1-(2,2- (ESI(+))dimethylbutanoyl)pyrrolidin- m/e 421 3- (M + H)⁺ yl]phenyl}-3-(pyridin-3- yl)azetidine-1- carboxamide 291 N-{4-[1-(2- (ESI(+))oxopropanoyl)pyrrolidin- m/e 393 3- (M + H)⁺ yl]phenyl}-3- (pyridin-3-yl)azetidine-1- carboxamide 292 N-{4-[1- (ESI(+))(methoxyacetyl)pyrrolidin- m/e 395 3- (M + H)⁺ yl]phenyl}-3- (pyridin-3-yl)azetidine-1- carboxamide 293 N-{4-[1- (ESI(+))(cyclohexylcarbonyl)pyrrolidin- m/e 433 3- (M + H)⁺ yl]phenyl}-3-(pyridin-3- yl)azetidine-1- carboxamide 294 N-{4-[1-(3- (ESI(+))methylbutanoyl)pyrrolidin- m/e 407 3- (M + H)⁺ yl]phenyl}-3- (pyridin-3-yl)azetidine-1- carboxamide 295 N-{4-[1- (ESI(+))(cyclopentylcarbonyl)pyrrolidin- m/e 419 3-yl]phenyl}-3- (M + H)⁺(pyridin-3- yl)azetidine-1- carboxamide 296 N-{4-[1-(2,3- (ESI(+))dimethylbutanoyl)pyrrolidin- m/e 421 3- (M + H)⁺ yl]phenyl}-3-(pyridin-3- yl)azetidine-1- carboxamide

Example 59 tert-butyl3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]pyrrolidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 3-(4-aminophenyl)pyrrolidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ8.56 (d, J=2.3 Hz, 1H), 8.52-8.45 (m, 2H), 7.86 (dt, J=7.9, 2.0 Hz, 1H),7.49-7.37 (m, 3H), 7.19-7.12 (m, 2H), 4.38 (d, J=16.3 Hz, 2H), 4.03-3.81(m, 3H), 3.66 (dd, J=10.1, 7.4 Hz, 1H), 3.51-3.40 (m, 1H), 3.29-3.19 (m,2H), 3.10 (t, J=9.8 Hz, 1H), 2.21-2.05 (m, 1H), 1.99-1.80 (m, 1H),1.43-1.38 (m, 8H), 1.26 (t, J=5.3 Hz, 1H); MS (ESI(+)) m/e 423 (M+H).

Example 60 tert-butyl(3R)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate

The title compound was prepared as in Example 1A-C, substituting(R)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate for tert-butyl3-hydroxyazetidine-1-carboxylate in Example 1A. ¹H NMR (300 MHz,DMSO-d₆) δ 8.56 (d, J=2.3 Hz, 1H), 8.48 (dd, J=4.8, 1.6 Hz, 1H), 8.37(s, 1H), 7.86 (dt, J=7.9, 2.0 Hz, 1H), 7.47-7.33 (m, 3H), 6.88-6.81 (m,2H), 4.90 (bs, 1H), 4.36 (d, J=16.0 Hz, 2H), 4.08-3.80 (m, 3H),3.57-3.33 (m, 1H), 2.11-1.96 (m, 2H), 1.42-1.36 (m, 9H); MS (ESI(+)) m/e439 (M+H).

Example 61 tert-butyl(3S)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate

The title compound was prepared as in Example 1A-C, substituting(S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate for tert-butyl3-hydroxyazetidine-1-carboxylate in Example 1A. ¹H NMR (300 MHz,DMSO-d₆) δ 8.56 (d, J=2.3 Hz, 1H), 8.48 (dd, J=4.8, 1.6 Hz, 1H), 8.37(s, 1H), 7.86 (dt, J=7.9, 2.0 Hz, 1H), 7.45-7.34 (m, 3H), 6.88-6.81 (m,2H), 4.90 (bs, 1H), 4.36 (d, J=16.0 Hz, 2H), 4.08-3.80 (m, 3H),3.58-3.31 (m, 1H), 2.11-1.96 (m, 2H), 1.42-1.36 (m, 9H); MS (ESI(+)) m/e439 (M+H).

Example 62 tert-butyl3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]azetidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 3-(4-aminophenyl)azetidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate. ¹H NMR (300 MHz, DMSO-d₆) δ8.57 (d, J=2.3 Hz, 1H), 8.51 (s, 1H), 8.53-8.45 (m, 2H), 7.87 (dt,J=7.9, 2.0 Hz, 1H), 7.53-7.46 (m, 2H), 7.41 (ddd, J=7.9, 4.7, 0.8 Hz,1H), 7.20 (d, J=8.6 Hz, 1H), 4.38 (d, J=16.4 Hz, 2H), 4.21 (t, J=8.1 Hz,2H), 4.13-3.63 (m, 6H), 1.40 (s, 9H); MS (ESI(+)) m/e 409 (M+H).

Example 63 tert-butyl3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]azetidine-1-carboxylate

The title compound was prepared as described in Example 1C. ¹H NMR (300MHz, DMSO-d₆) δ 8.56 (d, J=2.3 Hz, 1H), 8.48 (dd, J=4.7, 1.6 Hz, 1H),8.39 (s, 1H), 7.86 (dt, J=7.9, 2.0 Hz, 1H), 7.45-7.37 (m, 3H), 6.77-6.70(m, 2H), 4.96-4.85 (m, 1H), 4.36 (d, J=16.0 Hz, 2H), 4.31-4.22 (m, 2H),4.12-3.81 (m, 4H), 3.76 (dd, J=9.5, 3.9 Hz, 2H), 1.39 (s, 9H); MS(ESI(+)) m/e 425 (M+H).

Example 112 tert-butyl4-[4-({[3-(2-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate and3-(azetidin-3-yl)-2-chloropyridine for 3-(azetidin-3-yl)pyridine bishydrochloride. ¹H NMR (300 MHz, DMSO-d₆) δ 8.45 (s, 1H), 8.42-8.30 (m,1H), 8.01 (dd, J=7.7, 1.9 Hz, 1H), 7.56-7.42 (m, 2H), 7.44-7.37 (m, 2H),7.14-7.06 (m, 2H), 4.43-4.29 (m, 2H), 4.14-3.83 (m, 4H), 2.91-2.66 (m,2H), 1.76-1.59 (m, 2H), 1.47 (dd, J=12.6, 4.1 Hz, 1H), 1.41 (s, 10H),1.33-1.07 (m, 1H); MS (ESI(+)) m/e 415 (M+H)⁺.

Example 113 tert-butyl4-[4-({[3-(4-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate and3-(azetidin-3-yl)-4-chloropyridine for 3-(azetidin-3-yl)pyridine bishydrochloride. ¹H NMR (300 MHz, DMSO-d₆) δ 8.70 (s, 1H), 8.47 (d, J=5.3Hz, 2H), 8.47-8.43 (m, 2H), 7.57 (d, J=5.2 Hz, 1H), 7.45-7.38 (m, 2H),7.10 (d, J=8.6 Hz, 2H), 4.45-4.32 (m, 2H), 4.19-3.97 (m, 5H), 2.88-2.66(m, 2H), 1.77-1.66 (m, 2H), 1.41 (s, 10H); MS (ESI(+)) m/e 470 (M+H)⁺.

Example 116 tert-butyl4-[4-({[3-(2-fluoropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate and3-(azetidin-3-yl)-2-fluoropyridine for 3-(azetidin-3-yl)pyridine bishydrochloride. ¹H NMR (300 MHz, DMSO-d₆) δ 8.44 (s, 1H), 8.17-8.11 (m,1H), 8.09-7.99 (m, 1H), 7.48-7.30 (m, 3H), 7.10 (d, J=8.6 Hz, 2H),4.39-4.28 (m, 2H), 4.12-3.90 (m, 6H), 2.89-2.65 (m, 2H), 1.77-1.66 (m,2H), 1.41 (s, 11H); MS (ESI(+)) m/e 399 (M+H)⁺.

Example 157N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamideExample 157A N-(4-bromophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 13, substituting1-bromo-4-isocyanatobenzene for methyl 4-isocyanatobenzoate.

Example 157BN-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 9A, substituting1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolefor tert-butyl4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylateand N-(4-bromophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide for1-bromo-4-nitrobenzene. ¹H NMR (300 MHz, DMSO-d₆) δ 8.58 (t, J=3.4 Hz,1H), 8.53-8.43 (m, 1H), 8.04 (d, J=0.8 Hz, 1H), 7.92-7.83 (m, 1H),7.81-7.72 (m, 1H), 7.57-7.33 (m, 5H), 4.39 (t, J=8.2 Hz, 2H), 4.04-3.81(m, 6H), 2.21-2.03 (m, 1H), 0.89-0.82 (m, 6H); MS (ESI(+)) m/e 376(M+H)⁺.

Example 158N-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 157,substituting1-propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazolein Example 157B. ¹H NMR (500 MHz, DMSO-d₆) δ 8.60-8.55 (m, 1H), 8.52(bs, 1H), 8.49 (dd, J=4.7, 1.6 Hz, 1H), 8.06 (s, 1H), 7.92-7.84 (m, 1H),7.78 (s, 1H), 7.51 (d, J=8.7 Hz, 2H), 7.49-7.23 (m, 3H), 4.39 (t, J=8.4Hz, 2H), 4.05 (t, J=6.9 Hz, 2H), 3.97 (dt, J=17.7, 8.8 Hz, 2H),3.93-3.83 (m, 1H), 1.87-1.72 (m, 2H), 0.86 (s, 1H), 0.85 (s, 1H),0.86-0.80 (m, 1H); MS (ESI(+)) m/e 362 (M+H)⁺.

Example 1624-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)piperazine-1-carboxamideExample 162A 4-(piperidin-4-yloxy)aniline

The title compound was prepared as described in Example 1D, substitutingtert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate for tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate.

Example 162B1-(4-(4-aminophenoxy)piperidin-1-yl)-2-(tetrahydro-2H-pyran-4-yl)ethanone

The title compound was prepared as described in Example 1E, substituting4-(piperidin-4-yloxy)aniline forN-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamideand 2-(tetrahydro-2H-pyran-4-yl)acetic acid for (S)-2-methylbutanoicacid.

Example 162C4-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)piperazine-1-carboxamide

The title compound was prepared as described in Example 1C, substituting1-(4-(4-aminophenoxy)piperidin-1-yl)-2-(tetrahydro-2H-pyran-4-yl)ethanonefor tert-butyl 3-(4-aminophenoxy)azetidine-1-carboxylate and1-(pyridin-3-yl)piperazine for 3-(azetidin-3-yl)pyridine bishydrochloride. ¹H NMR (400 MHz, DMSO-d₆/D₂O) δ ppm 8.40-8.29 (m, 1H),8.12 (d, J=5.2 Hz, 1H), 7.97 (dd, J=8.9, 2.8 Hz, 1H), 7.77 (dd, J=8.9,5.3 Hz, 1H), 7.39-7.30 (m, 2H), 6.91-6.83 (m, 2H), 4.52-4.43 (m, 1H),3.86-3.73 (m, 4H), 3.65 (dd, J=11.2, 6.3 Hz, 4H), 3.52-3.41 (m, 4H),3.36-3.33 (m, 2H), 3.31-3.27 (m, 2H), 2.28 (d, J=6.9 Hz, 2H), 2.00-1.80(m, 4H), 1.71-1.49 (m, 4H), 1.36-1.16 (m, 2H); MS (ESI(+)) m/e 508(M+H)⁺.

Example 231N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamideExample 231A tert-butyl4-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate.

Example 231BN-(4-(piperidin-4-yl)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1D, substitutingtert-butyl4-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenyl)piperidine-1-carboxylatefor tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate.

Example 231CN-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide

In a 20 mL vial was addedN-(4-(piperidin-4-yl)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide,bistrifluoroacetic acid (67 mg, 0.12 mmol) dissolved in methanol, (2.0mL) followed by the addition of cyclopentanecarbaldehyde (13 mg, 0.13mmol) dissolved in methanol (0.45 mL), followed by the addition ofacetic acid neat (68 μL, 1.2 mmol). The reaction mixture was shaken for1 hour at 70° C. After that, MP-cyanoborohydride (272 mg, 2-3 mmol/g)resin was added and the resulting mixture was shaken at 70° C.overnight. The reaction mixture was filtered and concentrated todryness. The residues were dissolved in 1:1 DMSO/methanol and purifiedby reverse phase chromoatography. ¹H NMR (500 MHz, pyridine/d₅-D₂OTemp=90° C.) δ ppm 8.55 (dd, J=4.73, 1.68 Hz, 1 H) 8.40-8.48 (m, 1 H)7.75 (d, J=8.54 Hz, 2 H) 7.56-7.61 (m, 1 H) 7.21 (d, J=8.54 Hz, 2 H)7.16-7.19 (m, 1 H) 4.46 (t, J=8.24 Hz, 2 H) 4.10 (dd, J=8.09, 5.95 Hz, 2H) 3.64-3.74 (m, 1 H) 3.28 (d, 2 H) 2.39-2.66 (m, 5 H) 2.02-2.26 (m, 3H) 1.75-1.88 (m, 4 H) 1.40-1.59 (m, 4 H) 1.20-1.31 (m, 2 H); (ESI) m/z419 (M+H).

TABLE 4 The following Examples were prepared essentially as described inExample 231, substituting the appropriate amine in Example 231A and theappropriate aldehyde in Example 231C. Some products were purified byflash chromatography while others were purified by reverse-phase HPLC.Accordingly, some Examples were isolated as trifluoroacetic acid salts.Ex Name ¹H NMR MS 232 N-{4-[1- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp =90° C.) (ESI(+)) (cyclohexylmethyl)piperidin- ppm 8.55 (dd, J = 4.58,1.53 Hz, 1 H) m/e 433 4- 8.40-8.46 (m, 1 H) 7.75 (d, J = 8.54 Hz, 2 H)7.56-7.60 (m, 1 (M + H)⁺ yl]phenyl}-3- H) 7.21 (d, J = 8.54 Hz, 2 H)7.16-7.18 (m, 1 H) (pyridin-3- 4.46 (t, J = 8.24 Hz, 2 H) 4.05-4.15 (m,J = 7.93, 5.80 Hz, yl)azetidine- 2 H) 3.64-3.74 (m, 1 H) 3.16 (d, 2 H)1- 2.48-2.62 (m, 1 H) 2.37-2.43 (m, 2 H) 2.24-2.37 (m, 2 carboxamide H)1.94-2.11 (m, 2 H) 1.76-1.90 (m, 4 H) 1.53-1.72 (m, 4 H) 1.07-1.32 (m, 3H) 0.88-1.02 (m, 2 H) 233 N-{4-[1-(3,3- ¹H NMR (500 MHz, pyridine-d₅/D₂OTemp = 90° C.) (ESI(+)) dimethylbutyl)piperidin- ppm 8.55 (dd, J = 4.73,1.68 Hz, 1 H) m/e 421 4- 8.46-8.51 (m, 1 H) 7.75 (d, J = 8.54 Hz, 2 H)7.56-7.61 (m, 1 (M + H)⁺ yl]phenyl}-3- H) 7.21 (d, J = 8.54 Hz, 2 H)7.16-7.18 (m, 1 H) (pyridin-3- 4.46 (t, J = 8.24 Hz, 2 H) 4.02-4.16 (m,2 H) yl)azetidine- 3.64-3.75 (m, 1 H) 3.44 (d, J = 12.21 Hz, 2 H) 1-2.82-2.96 (m, 2 H) 2.53-2.69 (m, 3 H) 2.10-2.29 (m, 2 H) carboxamide1.81-1.97 (m, 2 H) 1.61-1.71 (m, 2 H) 0.89 (s, 9 H) 234 N-{4-[1-(2- ¹HNMR (500 MHz, pyridine-d₅/D₂O Temp = 90° C.) (ESI(+))methylpentyl)piperidin- ppm 8.55 (dd, J = 4.58, 1.53 Hz, 1 H) 8.42 (s, 1H) m/e 421 4- 7.75 (d, J = 8.54 Hz, 2 H) 7.55-7.60 (m, 1 H) (M + H)⁺yl]phenyl}-3- 7.20 (d, J = 8.54 Hz, 2 H) 7.16-7.18 (m, J = 5.19 Hz, 1 H)(pyridin-3- 4.46 (t, J = 8.24 Hz, 2 H) 4.07-4.12 (m, J = 7.93, 6.10 Hz,yl)azetidine- 2 H) 3.64-3.73 (m, 1 H) 2.99-3.08 (m, 2 H) 1- 2.43-2.54(m, 1 H) 2.05-2.33 (m, J = 12.51 Hz, 4 carboxamide H) 1.67-1.97 (m, 5 H)1.24-1.50 (m, 3 H) 1.05-1.18 (m, J = 9.46 Hz, 1 H) 0.95 (d, J = 6.71 Hz,3 H) 0.89 (t, J = 7.17 Hz, 3 H) 235 N-{4-[1-(2- ¹H NMR (500 MHz,pyridine-d₅/D₂O Temp = 90° C.) (ESI(+)) methylpropyl)piperidin- ppm 8.55(dd, J = 4.73, 1.68 Hz, 1 H) m/e 393 4- 8.41-8.43 (m, 1 H) 7.75 (d, J =8.54 Hz, 2 H) 7.56-7.61 (m, 1 (M + H)⁺ yl]phenyl}-3- H) 7.20 (d, J =8.54 Hz, 2 H) 7.16-7.18 (m, J = 4.58 Hz, (pyridin-3- 1 H) 4.46 (t, J =8.39 Hz, 2 H) 4.08-4.12 (m, 2 yl)azetidine- H) 3.65-3.73 (m, 1 H) 3.00(d, 2 H) 2.43-2.54 (m, 1- 1 H) 2.19 (d, J = 7.02 Hz, 2 H) 2.07-2.17 (m,2 H) carboxamide 1.73-1.94 (m, 5 H) 0.92 (d, J = 6.71 Hz, 6 H) 236N-{4-[1-(3- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = 90° C.) (ESI(+))methylbutyl)piperidin- ppm 8.55 (dd, J = 4.88, 1.53 Hz, 1 H) m/e 407 4-8.44-8.49 (m, 1 H) 7.75 (d, J = 8.54 Hz, 2 H) 7.56-7.60 (m, 1 (M + H)⁺yl]phenyl}-3- H) 7.21 (d, J = 8.54 Hz, 2 H) 7.16-7.18 (m, J = 4.88 Hz,(pyridin-3- 1 H) 4.46-4.48 (m, 2 H) 4.10 (dd, J = 7.93, 5.80 Hz,yl)azetidine- 2 H) 3.64-3.73 (m, 1 H) 3.31 (d, J = 12.21 Hz, 2 1- H)2.68-2.75 (m, 2 H) 2.53-2.64 (m, 1 H) carboxamide 2.41-2.51 (m, 2 H)2.01-2.17 (m, 2 H) 1.87 (d, 2 H) 1.51-1.63 (m, 3 H) 0.87 (d, J = 6.10Hz, 6 H) 237 N-{4-[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = 90° C.)(ESI(+)) ethylbutyl)piperidin- ppm 8.55 (dd, J = 4.58, 1.53 Hz, 1 H) m/e421 4- 8.40-8.48 (m, 1 H) 7.75 (d, J = 8.54 Hz, 2 H) 7.56-7.61 (m, 1(M + H)⁺ yl]phenyl}-3- H) 7.21 (d, J = 8.54 Hz, 2 H) 7.16-7.18 (m, 1 H)(pyridin-3- 4.46 (t, J = 8.39 Hz, 2 H) 4.10 (dd, J = 7.93, 6.10 Hz, 2yl)azetidine- H) 3.64-3.74 (m, 1 H) 3.14 (d, 2 H) 2.47-2.62 (m, 1- 1 H)2.37-2.43 (m, 2 H) 2.22-2.32 (m, 2 H) carboxamide 1.93-2.06 (m, 2 H)1.77-1.85 (m, 2 H) 1.50-1.63 (m, 1 H) 1.30-1.50 (m, 4 H) 0.88 (t, J =7.32 Hz, 6 H) 238 N-{4-[1-(2,2- (ESI(+)) dimethylpropyl)piperidin- m/e407 4-yl]phenyl}- (M + H)⁺ 3-(pyridin-3- yl)azetidine- 1- carboxamide239 N-{4-[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = 90° C.) (ESI(+))methylbutyl)piperidin- ppm 8.55 (d, J = 4.58 Hz, 1 H) 8.42 (s, 1 H) m/e407 4- 7.75 (d, J = 8.54 Hz, 2 H) 7.56-7.61 (m, 1 H) (M + H)⁺yl]phenyl}-3- 7.31-7.36 (m, 1 H) 7.20 (d, J = 8.54 Hz, 2 H) 4.46 (t, J =8.39 Hz, (pyridin-3- 2 H) 4.07-4.12 (m, J = 8.09, 5.95 Hz, 2 H)yl)azetidine- 3.63-3.76 (m, 1 H) 2.90-3.02 (m, 2 H) 2.42-2.52 (m, 1- 1H)2.16-2.27 (m, 1 H) 1.95-2.13 (m, 3 H) carboxamide 1.73-1.86 (m, J = 3.66Hz, 4 H) 1.42-1.64 (m, J = 49.13 Hz, 2 H) 1.07-1.23 (m, 1 H) 0.85-0.96(m, 6 H) 240 N-[4-(1- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = 90° C.)(ESI(+)) butylpiperidin- ppm 8.55 (dd, J = 4.58, 1.53 Hz, 1 H) m/e 3934- 8.42-8.48 (m, 1 H) 7.75 (d, J = 8.24 Hz, 2 H) 7.56-7.61 (m, 1 (M +H)⁺ yl)phenyl]-3- H) 7.20 (d, J = 8.54 Hz, 2 H) 7.16-7.18 (m, 1 H)(pyridin-3- 4.46 (t, J = 8.24 Hz, 2 H) 4.10 (dd, J = 8.09, 5.95 Hz, 2yl)azetidine- H) 3.63-3.75 (m, 1 H) 3.24 (d, 2 H) 2.49-2.69 (m, 1- 3 H)2.32-2.41 (m, 2 H) 1.98-2.16 (m, 2 H) carboxamide 1.78-1.87 (m, 2 H)1.53-1.66 (m, 2 H) 1.24-1.37 (m, 2 H) 0.86 (t, 3 H) 241 N-[4-(1- ¹H NMR(500 MHz, pyridine-d₅/D₂O Temp = 90° C.) (ESI(+)) propylpiperidin- ppm8.55 (dd, J = 4.58, 1.53 Hz, 1 H) m/e 379 4- 8.44-8.49 (m, 1 H) 7.76 (d,J = 8.70 Hz, 2 H) 7.56-7.62 (m, 1 (M + H)⁺ yl)phenyl]-3- H) 7.20 (d, J =8.54 Hz, 2 H) 7.16-7.18 (m, J = 5.49 Hz, (pyridin-3- 1 H) 4.46 (t, J =8.39 Hz, 2 H) 4.04-4.16 (m, 2 yl)azetidine- H) 3.64-3.73 (m, 1 H)3.26-3.36 (m, 2 H) 1- 2.43-2.72 (m, 5 H) 2.04-2.20 (m, 2 H) 1.85 (d, 2H) carboxamide 1.57-1.72 (m, 2 H) 0.84 (t, J = 7.32 Hz, 3 H) 242N-{4-[1-(2- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = 90° C.) (ESI(+))cyclopropylethyl)piperidin- ppm 8.55 (dd, J = 4.73, 1.37 Hz, 1 H) m/e405 4-yl]phenyl}- 8.43-8.48 (m, 1 H) 7.75 (d, J = 8.24 Hz, 2 H) 7.58 (d,J = 7.93 Hz, (M + H)⁺ 3-(pyridin-3- 1 H) 7.18 (d, 2 H) 7.16-7.17 (m, 1H) yl)azetidine- 4.33-4.38 (m, 2 H) 4.05-4.14 (m, J = 8.09, 5.95 Hz, 2H) 1- 3.62-3.77 (m, 1 H) 3.23-3.35 (m, 2 H) carboxamide 2.75-2.86 (m, 2H) 2.42-2.64 (m, 3 H) 2.00-2.18 (m, 2 H) 1.80-1.90 (m, 2 H) 1.53-1.63(m, 2 H) 0.58-0.72 (m, 1 H) 0.36-0.44 (m, 2 H) 0.07 (q, J = 4.88 Hz, 2H) 243 3-(pyridin-3- ¹H NMR (500 MHz, pyridine-d₅/D₂O Temp = 90° C.)(ESI(+)) yl)-N-{4-[1- ppm 8.55 (dd, J = 4.88, 1.53 Hz, 1 H) 8.43 (s, 1H) m/e 421 (tetrahydrofuran- 7.75 (d, J = 8.24 Hz, 2 H) 7.56-7.62 (m, 1H) (M + H)⁺ 3- 7.20 (d, J = 8.54 Hz, 2 H) 7.16-7.17 (m, 1 H) 4.46 (t,ylmethyl)piperidin- J = 8.24 Hz, 2 H) 4.10 (dd, J = 7.93, 5.80 Hz, 2 H)4- 3.87-3.93 (m, J = 8.24, 6.71 Hz, 1 H) yl]phenyl}azetidine- 3.76-3.85(m, 1 H) 3.65-3.73 (m, 2 H) 3.57 (dd, J = 8.39, 5.65 Hz, 1- 1 H)2.96-3.11 (m, 2 H) 2.39-2.55 (m, 4 H) carboxamide 2.09-2.21 (m, 2 H)1.72-2.01 (m, 5 H) 1.50-1.63 (m, 1 H) 244 N-{4-[1-(2,2- ¹H NMR (500 MHz,pyridine-d₅/D₂O Temp = 90° C.) (ESI(+)) dimethylbutyl)piperidin- ppm8.55 (dd, J = 4.88, 1.53 Hz, 1 H) 8.42 (s, 1 H) m/e 421 4- 7.76 (d, J =8.54 Hz, 2 H) 7.56-7.62 (m, 1 H) (M + H)⁺ yl]phenyl}-3- 7.20 (d, J =8.54 Hz, 2 H) 7.16-7.18 (m, J = 4.88 Hz, 1 H) (pyridin-3- 4.46 (t, J =8.39 Hz, 2 H) 4.07-4.14 (m, 2 H) yl)azetidine- 3.65-3.75 (m, 1 H) 2.90(d, J = 11.90 Hz, 2 H) 1- 2.40-2.45 (m, 1 H) 2.25-2.37 (m, 2 H) 2.12 (s,2 H) carboxamide 1.67-1.91 (m, 4 H) 1.30 (q, J = 7.43 Hz, 2 H) 0.87 (s,6 H) 0.83 (t, J = 7.63 Hz, 3 H) 245 N-{4-[1- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) (cyclopentylmethyl)azetidin- ppm8.60 (d, J = 2.14 Hz, 1 H) 8.52 (dd, J = 5.04, m/e 391 3- 1.37 Hz, 1 H)7.94 (d, J = 7.63 Hz, 1 H) (M + H)⁺ yl]phenyl}-3- 7.48-7.54 (m, 3 H)7.27 (d, J = 8.54 Hz, 2 H) 3.88-4.54 (m, 10 (pyridin-3- H) 3.18-3.23 (m,2 H) 2.09 (d, J = 7.63 Hz, 1 H) yl)azetidine- 1.78 (s, 2 H) 1.47-1.69(m, 4 H) 1.15-1.29 (m, 2 1- H) carboxamide 246 N-{4-[1- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) (cyclohexylmethyl)azetidin- ppm 8.62(d, J = 2.14 Hz, 1 H) 8.54 (dd, J = 4.88, m/e 405 3- 1.22 Hz, 1 H) 7.99(d, J = 7.93 Hz, 1 H) (M + H)⁺ yl]phenyl}-3- 7.47-7.59 (m, 3 H) 7.26 (d,J = 8.54 Hz, 2 H) 3.73-4.68 (m, 10 (pyridin-3- H) 3.11 (s, 2 H)1.54-1.78 (m, 6 H) 1.10-1.37 (m, yl)azetidine- 3 H) 0.92-1.07 (m, J =9.77 Hz, 2 H) 1- carboxamide 247 N-{4-[1-(3,3- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) dimethylbutyl)azetidin- ppm 8.64 (d,J = 2.14 Hz, 1 H) 8.56 (d, J = 4.88 Hz, m/e 393 3- 1 H) 8.05 (d, J =7.93 Hz, 1 H) 7.60 (dd, J = 7.78, 5.04 Hz, (M + H)⁺ yl]phenyl}-3- 1 H)7.51 (d, J = 8.54 Hz, 2 H) 7.26 (t, J = 7.78 Hz, (pyridin-3- 2 H)3.88-4.53 (m, 10 H) 3.12-3.24 (m, 2 H) yl)azetidine- 1.35-1.47 (m, 2 H)0.93 (s, 9 H) 1- carboxamide 248 N-{4-[1- ¹H NMR (400 MHz, DMSO-d₆/D₂OTemp = 90° C.) (ESI(+)) (cyclopropylmethyl)azetidin- ppm 8.63 (d, J =2.14 Hz, 1 H) 8.52-8.55 (m, 1 m/e 363 3- H) 7.95-8.04 (m, 1 H) 7.57 (dd,J = 7.93, 5.19 Hz, 1 (M + H)⁺ yl]phenyl}-3- H) 7.51 (d, J = 8.54 Hz, 2H) 7.27 (d, J = 8.54 Hz, 2 (pyridin-3- H) 3.90-4.51 (m, 10 H) 3.13 (s, 2H) yl)azetidine- 0.95-1.07 (m, 1 H) 0.58-0.67 (m, 2 H) 0.35-0.43 (m, 1-J = 5.04, 5.04 Hz, 2 H) carboxamide 249 N-{4-[1-(2- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) methylpentyl)azetidin- ppm 8.60 (d,J = 2.44 Hz, 1 H) 8.49-8.53 (m, 1 m/e 393 3- H) 7.95 (d, J = 7.93 Hz, 1H) 7.45-7.56 (m, 3 H) (M + H)⁺ yl]phenyl}-3- 7.23-7.31 (m, 2 H)4.23-4.59 (m, 5 H) (pyridin-3- 3.86-4.24 (m, 6 H) 2.98-3.24 (m, 1 H)1.72-1.87 (m, 1 H) yl)azetidine- 1.10-1.46 (m, 4 H) 0.83-0.96 (m, 6 H)1- carboxamide 250 3-(pyridin-3- (ESI(+)) yl)-N-{4-[1- m/e 393(tetrahydrofuran- (M + H)⁺ 2- ylmethyl)azetidin- 3- yl]phenyl}azetidine-1- carboxamide 251 N-{4-[1-(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90°C.) (ESI(+)) methylpropyl)azetidin- ppm 8.60 (d, J = 2.14 Hz, 1 H)8.50-8.53 (m, 1 m/e 365 3- H) 7.92-7.97 (m, 1 H) 7.47-7.56 (m, 3 H) 7.27(d, (M + H)⁺ yl]phenyl}-3- J = 8.54 Hz, 2 H) 4.25-4.54 (m, 5 H)3.92-4.14 (m, (pyridin-3- 5 H) 3.06-3.17 (m, 2 H) 1.88-1.97 (m, J = 7.02Hz, yl)azetidine- 1 H) 0.96 (d, J = 6.71 Hz, 6 H) 1- carboxamide 252N-{4-[1-(3- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))methylbutyl)azetidin- ppm 8.61 (d, J = 2.14 Hz, 1 H) 8.53 (d, J = 4.58Hz, m/e 379 3- 1 H) 7.98 (d, J = 7.93 Hz, 1 H) 7.47-7.57 (m, 3 H) (M +H)⁺ yl]phenyl}-3- 7.26 (d, J = 8.54 Hz, 2 H) 3.86-4.53 (m, 10 H)(pyridin-3- 3.16-3.22 (m, 2 H) 1.56-1.74 (m, 1 H) 1.37-1.48 (m,yl)azetidine- 2 H) 0.92 (d, J = 6.71 Hz, 6 H) 1- carboxamide 253N-{4-[1-(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))ethylbutyl)azetidin- ppm 8.66 (d, J = 2.14 Hz, 1 H) 8.57 (dd, J = 5.04,m/e 393 3- 1.37 Hz, 1 H) 8.09 (d, J = 7.93 Hz, 1 H) 7.63 (dd, (M + H)⁺yl]phenyl}-3- J = 8.09, 5.04 Hz, 1 H) 7.51 (d, J = 8.54 Hz, 2 H)(pyridin-3- 7.26 (t, J = 8.09 Hz, 2 H) 3.88-4.54 (m, 10 H) yl)azetidine-3.09-3.24 (m, 2 H) 1.50-1.62 (m, 1 H) 1.27-1.45 (m, 4 H) 1- 0.88 (t, J =7.48 Hz, 6 H) carboxamide 254 N-{4-[1-(2,2- ¹H NMR (400 MHz, DMSO-d₆/D₂OTemp = 90° C.) (ESI(+)) dimethylpropyl)azetidin- ppm 8.66 (d, J = 2.14Hz, 1 H) 8.58 (dd, J = 5.04, m/e 379 3- 1.37 Hz, 1 H) 8.10 (d, J = 7.93Hz, 1 H) 7.64 (dd, (M + H)⁺ yl]phenyl}-3- J = 7.93, 5.19 Hz, 1 H)7.43-7.58 (m, 2 H) (pyridin-3- 7.20-7.33 (m, 2 H) 4.29-4.65 (m, 5 H)3.85-4.19 (m, 5 yl)azetidine- H) 3.13-3.20 (m, 2 H) 1.00 (s, 9 H) 1-carboxamide 255 N-{4-[1-(2- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.)(ESI(+)) methylbutyl)azetidin- ppm 8.57 (d, J = 1.83 Hz, 1 H) 8.49 (d,m/e 379 3- J = 3.66 Hz, 1 H) 7.84-7.90 (m, 1 H) 7.42-7.53 (m, (M + H)⁺yl]phenyl}-3- 3 H) 7.27 (d, J = 8.54 Hz, 2 H) 3.84-4.56 (m, 11 H)(pyridin-3- 3.00-3.19 (m, 1 H) 1.61-1.83 (m, 1 H) yl)azetidine-1.11-1.49 (m, J = 64.70 Hz, 2 H) 0.85-0.97 (m, 6 H) 1- carboxamide 2563-(pyridin-3- ¹H NMR (400 MHz, DMSO-d₆/D₂O Temp = 90° C.) (ESI(+))yl)-N-{4-[1- ppm 8.66 (d, J = 2.14 Hz, 1 H) 8.58 (dd, m/e 393(tetrahydrofuran- J = 5.04, 1.37 Hz, 1 H) 8.10 (d, J = 8.24 Hz, 1 H)(M + H)⁺ 3- 7.64 (dd, J = 8.09, 5.04 Hz, 1 H) 7.51 (d, J = 8.24 Hz, 2 H)ylmethyl)azetidin- 7.27 (d, J = 8.54 Hz, 2 H) 3.94-4.60 (m, 10 H) 3-3.72-3.84 (m, 2 H) 3.62-3.70 (m, 1 H) 3.38-3.47 (m, yl]phenyl}azetidine-1 H) 3.31 (d, J = 7.02 Hz, 2 H) 2.39-2.50 (m, 1 H) 1- 2.00-2.16 (m, 1 H)1.54-1.72 (m, 1 H) carboxamide 257 N-{4-[1-(2,2- ¹H NMR (400 MHz,DMSO-d₆/D₂O Temp = 90° C.) (ESI(+)) dimethylbutyl)azetidin- ppm 8.70 (d,J = 1.83 Hz, 1 H) 8.61 (d, J = 5.19 Hz, m/e 393 3- 1 H) 8.19 (d, J =7.94 Hz, 1 H) 7.72 (dd, J = 7.78, 5.34 Hz, (M + H)⁺ yl]phenyl}-3- 1 H)7.50 (s, 2 H) 7.28 (d, J = 8.54 Hz, 2 H) (pyridin-3- 3.93-4.63 (m, 10 H)3.18 (s, 2 H) 1.32 (q, J = 7.43 Hz, 2 yl)azetidine- H) 0.95 (s, 6 H)0.84 (t, J = 7.48 Hz, 3 H) 1- carboxamide

Example 336N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamideExample 336A tert-butyl4-(4-(3-(pyridazin-3-yl)azetidine-1-carboxamido)phenyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate and3-(azetidin-3-yl)pyridazine hydrochloride for 3-(azetidin-3-yl)pyridinebis hydrochloride.

Example 336BN-(4-(piperidin-4-yl)phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1D, substitutingtert-butyl4-(4-(3-(pyridazin-3-yl)azetidine-1-carboxamido)phenyl)piperidine-1-carboxylatefor tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate.

Example 336CN-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1E, substitutingN-(4-(piperidin-4-yl)phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamideforN-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamideand benzoic acid for (S)-2-methylbutanoic acid. ¹H NMR (400 MHz, DMSO) δ9.16 (dd, J=4.5, 2.0 Hz, 1H), 8.48 (s, 1H), 7.77-7.61 (m, 2H), 7.54-7.36(m, 7H), 7.18-7.12 (m, 2H), 4.74-4.49 (m, 1H), 4.38 (t, J=8.1 Hz, 2H),4.27-4.08 (m, 3H), 3.69-3.55 (m, 1H), 3.26-2.65 (m, 3H), 1.93-1.48 (m,4H); MS (ESI(+)) m/e 442 (M+H)⁺.

TABLE 5 The following Examples were essentially prepared as described inExample 336, substituting an appropriate carboxylic acid in Example336C. Ex Name MS 337 N-{4-[1-(2-fluorobenzoyl)piperidin- (ESI(+))4-yl]phenyl}-3-(pyridazin-3- m/e 460 yl)azetidine-1-carboxamide (M + H)⁺338 N-{4-[1-(2-methylbenzoyl)piperidin- (ESI(+))4-yl]phenyl}-3-(pyridazin-3- m/e 456 yl)azetidine-1-carboxamide (M + H)⁺339 N-{4-[1-(2,2-dimethylpropanoyl)piperidin- (ESI(+))4-yl]phenyl}-3-(pyridazin-3- m/e 422 yl)azetidine-1-carboxamide (M + H)⁺340 N-{4-[1-(cyclopropylcarbonyl)piperidin- (ESI(+))4-yl]phenyl}-3-(pyridazin- m/e 406 3-yl)azetidine-1-carboxamide (M + H)⁺341 N-[4-(1-acetylpiperidin-4- (ESI(+)) yl)phenyl]-3-(pyridazin-3- m/e380 yl)azetidine-1-carboxamide (M + H)⁺ 342N-{4-[1-(3,3-dimethylbutanoyl)piperidin- (ESI(+))4-yl]phenyl}-3-(pyridazin- m/e 436 3-yl)azetidine-1-carboxamide (M + H)⁺343 N-{4-[1-(cyclobutylcarbonyl)piperidin- (ESI(+))4-yl]phenyl}-3-(pyridazin-3- m/e 420 yl)azetidine-1-carboxamide (M + H)⁺344 3-(pyridazin-3-yl)-N-{4-[1-(4,4,4- (ESI(+))trifluorobutanoyl)piperidin-4- m/e 462 yl]phenyl}azetidine-1-carboxamide(M + H)⁺ 345 3-(pyridazin-3-yl)-N-{4-[1-(3,3,3- (ESI(+))trifluoropropanoyl)piperidin-4- m/e 448yl]phenyl}azetidine-1-carboxamide (M + H)⁺ 346N-(4-{1-[(1-methylcyclopropyl)- (ESI(+))carbonyl]piperidin-4-yl}phenyl)-3- m/e 420(pyridazin-3-yl)azetidine-1-carboxamide (M + H)⁺ 347N-{4-[1-(cyclopropylacetyl)piperidin- (ESI(+))4-yl]phenyl}-3-(pyridazin-3- m/e 420 yl)azetidine-1-carboxamide (M + H)⁺

Example 348N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamideExample 348A 4-(pyridin-4-ylmethyl)aniline

The title compound was prepared as described in Example 1B, substituting4-(4-nitrobenzyl)pyridine for tert-butyl3-(4-nitrophenoxy)azetidine-1-carboxylate.

Example 348B 2,2,2-trifluoro-N-(4-(pyridin-4-ylmethyl)phenyl)acetamide

A solution of 4-(pyridin-4-ylmethyl)aniline (21.6 g, 117 mmol) andtriethylamine (19.61 ml, 141 mmol) in dichloromethane (586 ml) wascooled to 0° C. Trifluoroacetic anhydride (19.87 ml, 141 mmol) was addeddropwise via additional funnel over a period of 20 minutes. The mixturewas stirred at 0° C. for 1 hour and then at room temperature for 2hours. The reaction mixture was then concentrated in vacuo and theresulting residue was purified by regular phase column chromatography togive the title compound.

Example 348C 2,2,2-trifluoro-N-(4-(piperidin-4-ylmethyl)phenyl)acetamide

2,2,2-Trifluoro-N-(4-(pyridin-4-ylmethyl)phenyl)acetamide (28.5 g, 102mmol) and acetic acid (205 ml) were added to platinum(IV) oxide (3.42 g,15.06 mmol) in a 500 mL stainless steel pressure bottle and the mixturewas stirred for 16 hours at 40 psi. The mixture was filtered through anylon membrane and concentrated in vacuo; and the resulting residue wastaken up in methanol (100 mL) and poured into diethyl ether (600 mL).The precipitate was filtered, washed with ether and dried to afford thetitle compound.

Example 348D tert-butyl 4-(4-aminobenzyl)piperidine-1-carboxylate

A solution of2,2,2-trifluoro-N-(4-(piperidin-4-ylmethyl)phenyl)acetamide (26.4 g, 92mmol) in dichloromethane (369 ml) was cooled to 0° C. and triethylamine(19.28 ml, 138 mmol) was added slowly. To the resulting solution wasadded di-tert-butyl dicarbonate (22.14 g, 101 mmol) in dichloromethane(75 ml) via addition funnel over 10 minutes. The 0° C. mixture wasstirred for 2 hours and warmed slowly overnight. The reaction mixturewas recooled to 0° C., treated with 1 N sodium hydroxide (100 ml),warmed to room temperature and stirred for 1 hour. The bilayer wasseparated and the organics were washed with water and brine, dried withmagnesium sulfate, filtered and concentrated in vacuo. The residue waspurified by normal phase chromatography to give the title compound.

Example 348E tert-butyl4-(4-(3-(pyridazin-3-yl)azetidine-1-carboxamido)benzyl)piperidine-1-carboxylate

The title compound was prepared as described in Example 1C, substitutingtert-butyl 4-(4-aminobenzyl)piperidine-1-carboxylate for tert-butyl3-(4-aminophenoxy)azetidine-1-carboxylate and3-(azetidin-3-yl)pyridazine hydrochloride for 3-(azetidin-3-yl)pyridinebis hydrochloride.

Example 348FN-(4-(piperidin-4-ylmethyl)phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1D, substitutingtert-butyl4-(4-(3-(pyridazin-3-yl)azetidine-1-carboxamido)benzyl)piperidine-1-carboxylatefor tert-butyl3-(4-(3-(pyridin-3-yl)azetidine-1-carboxamido)phenoxy)azetidine-1-carboxylate.

Example 348GN-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide

The title compound was prepared as described in Example 1E, substitutingN-(4-(piperidin-4-ylmethyl)phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamideforN-(4-(azetidin-3-yloxy)phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamideand benzoic acid for (S)-2-methylbutanoic acid. ¹H NMR (400 MHz, DMSO) δ9.16 (dd, J=4.5, 2.0 Hz, 1H), 8.45 (s, 1H), 7.70 (qd, J=8.5, 3.3 Hz,2H), 7.43 (dt, J=12.3, 6.2 Hz, 5H), 7.38-7.27 (m, 2H), 7.04 (d, J=8.5Hz, 2H), 4.51-4.31 (m, 3H), 4.26-4.06 (m, 3H), 3.54 (s, 1H), 2.83 (d,J=96.4 Hz, 2H), 2.46 (d, J=6.7 Hz, 2H), 1.83-1.41 (m, 3H), 1.11 (s, 2H),MS (ESI(+)) m/e 456 (M+H)⁺.

TABLE 6 The following Examples were essentially prepared as described inExample 1, substituting 1,3-dihydro-2H-pyrrolo[3,4-c]pyridine forisoindoline in Example 1A and using an appropriate amine as described inExample 1C. Ex Name MS 349 N-(4-{[1-(2-fluorobenzoyl)piperidin-4-(ESI(+)) yl]methyl}phenyl)-3-(pyridazin- m/e 4743-yl)azetidine-1-carboxamide (M + H)⁺ 350N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4- (ESI(+))yl]methyl}phenyl)-3-(pyridazin- m/e 474 3-yl)azetidine-1-carboxamide(M + H)⁺ 351 N-(4-{[1-(3,3-dimethylbutanoyl)piperidin- (ESI(+))4-yl]methyl}phenyl)-3-(pyridazin- m/e 450 3-yl)azetidine-1-carboxamide(M + H)⁺ 352 N-(4-{[1-(2-ethylbutanoyl)piperidin-4- (ESI(+))yl]methyl}phenyl)-3-(pyridazin- m/e 450 3-yl)azetidine-1-carboxamide(M + H)⁺ 353 3-(pyridazin-3-yl)-N-(4-{[1-(4,4,4- (ESI(+))trifluorobutanoyl)piperidin-4-yl]methyl}- m/e 476phenyl)azetidine-1-carboxamide (M + H)⁺ 354N-(4-{[1-(2-methylpropanoyl)piperidin- (ESI(+))4-yl]methyl}phenyl)-3-(pyridazin- m/e 422 3-yl)azetidine-1-carboxamide(M + H)⁺ 355 N-{4-[(1-acetylpiperidin-4- (ESI(+))yl)methyl]phenyl}-3-(pyridazin-3- m/e 394 yl)azetidine-1-carboxamide(M + H)⁺ 356 N-[4-({1-[(2S)-2-methylbutanoyl]piperidin- (ESI(+))4-yl}methyl)phenyl]-3- m/e 436 (pyridazin-3-yl)azetidine-1-carboxamide(M + H)⁺ 357 N-[4-({1-[(1-methylcyclopropyl)- (ESI(+))carbonyl]piperidin-4-yl}methyl)phenyl]- m/e 4343-(pyridazin-3-yl)azetidine-1-carboxamide (M + H)⁺

What is claimed is:
 1. A compound of formula (IA), or a therapeuticallyacceptable salt thereof,

wherein X¹ is N and X² is CR¹; or X¹ is CR¹ and X² is N; or X¹ is CR¹and X² is CR¹; Y¹ is

wherein

indicates the point of attachment to the carbonyl and

indicates the point of attachment to the nitrogen containing heteroaryl;R¹, at each occurrence, is independently selected from the groupconsisting of hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydoxyalkyl,alkoxy, OH, NH₂, CN, NO₂, F, Cl, Br and I; R² is independently selectedfrom the group consisting of C₄-C₆-alkyl, C₄-C₆-alkenyl, C₄-C₆-alkynyl,aryl, 3-12 membered heterocyclyl, cycloalkyl, and cycloalkenyl; whereineach R² C₄-C₆-alkyl, C₄-C₆-alkenyl, and C₄-C₆-alkynyl is substitutedwith one or more substituents independently selected from the groupconsisting of R³, OR³, SR³, S(O)R³, SO₂R³, C(O)R³, CO(O)R³, OC(O)R³,OC(O)OR³, NH₂, NHR³, N(R³)₂, NHC(O)R³, NR³C(O)R³, NHS(O)₂R³, NR³S(O)₂R³,NHC(O)OR³, NR³C(O)OR³, NHC(O)NH₂, NHC(O)NHR³, NHC(O)N(R³)₂, NR³C(O)NHR³,NR³C(O)N(R³)₂, C(O)NH₂, C(O)NHR³, C(O)N(R³)₂, C(O)NHOH, C(O)NHOR³,C(O)NHSO₂R³, C(O)NR³SO₂R³, SO₂NH₂, SO₂NHR³, SO₂N(R³)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR³, C(N)N(R³)₂, CNOH, CNOCH₃, OH,(O), CN, N₃, NO₂, F, Cl,Br and I; wherein each R² aryl, 3-12 membered heterocyclyl, cycloalkyl,and cycloalkenyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁴, OR⁴, SR⁴,S(O)R⁴, SO₂R⁴, C(O)R⁴, CO(O)R⁴, OC(O)R⁴, OC(O)OR⁴, NH₂, NHR⁴, N(R⁴)₂,NHC(O)R⁴, NR⁴C(O)R⁴, NHS(O)₂R⁴, NR⁴S(O)₂R⁴, NHC(O)OR⁴, NR⁴C(O)OR⁴,NHC(O)NH₂, NHC(O)NHR⁴, NHC(O)N(R⁴)₂, NR⁴C(O)NHR⁴, NR⁴C(O)N(R⁴)₂,C(O)NH₂, C(O)NHR⁴, C(O)N(R⁴)₂, C(O)NHOH, C(O)NHOR⁴, C(O)NHSO₂R⁴,C(O)NR⁴SO₂R⁴, SO₂NH₂, SO₂NHR⁴, SO₂N(R⁴)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR⁴, C(N)N(R⁴)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;R³, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl,and heterocyclyl; wherein each R³ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁵, OR⁵, SR⁵, S(O)R⁵, SO₂R⁵,C(O)R⁵, CO(O)R⁵, OC(O)R⁵, OC(O)OR⁵, NH₂, NHR⁵, N(R⁵)₂, NHC(O)R⁵,NR⁵C(O)R⁵, NHS(O)₂R⁵, NR⁵S(O)₂R⁵, NHC(O)OR⁵, NR⁵C(O)OR⁵, NHC(O)NH₂,NHC(O)NHR⁵, NHC(O)N(R⁵)₂, NR⁵C(O)NHR⁵, NR⁵C(O)N(R⁵)₂, C(O)NH₂, C(O)NHR⁵, C(O)N(R⁵)₂, C(O)NHOH, C(O)NHOR⁵, C(O)NHSO₂R⁵, C(O)NR⁵SO₂R⁵, SO₂NH₂,SO₂NHR⁵, SO₂N(R⁵)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁵, C(N)N(R⁵)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein each R³ aryl,cycloalkyl, cycloalkenyl, and heterocyclyl is optionally substitutedwith one or more substituents independently selected from the groupconsisting of R⁶, OR⁶, SR⁶, S(O)R⁶, SO₂R⁶, C(O)R⁶, CO(O)R⁶, OC(O)R⁶,OC(O)OR⁶, NH₂, NHR⁶, N(R⁶)₂, NHC(O)R⁶, NR⁶C(O)R⁶, NHS(O)₂R⁶, NR⁶S(O)₂R⁶,NHC(O)OR⁶, NR⁶C(O)OR⁶, NHC(O)NH₂, NHC(O)NHR⁶, NHC(O)N(R⁶)₂, NR⁶C(O)NHR⁶,NR⁶C(O)N(R⁶)₂, C(O)NH₂, C(O)NHR⁶, C(O)N(R⁶)₂, C(O)NHOH, C(O)NHOR⁶,C(O)NHSO₂R⁶, C(O)NR⁶SO₂R⁶, SO₂NH₂, SO₂NHR⁶, SO₂N(R⁶)₂, C(O)H, C(O)OH,C(N)NH₂, C(N)NHR⁶, C(N)N(R⁶)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Brand I; R⁴, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R⁴ alkyl, alkenyl, and alkynyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of R⁷, OR⁷, SR⁷, S(O)R⁷, SO₂R⁷,C(O)R⁷, CO(O)R⁷, OC(O)R⁷, OC(O)OR⁷, NH₂, NHR⁷, N(R⁷)₂, NHC(O)R⁷,NR⁷C(O)R⁷, NHS(O)₂R⁷, NR⁷S(O)₂R⁷, NHC(O)OR⁷, NR⁷C(O)OR⁷, NHC(O)NH₂,NHC(O)NHR⁷, NHC(O)N(R⁷)₂, NR⁷C(O)NHR⁷, NR⁷C(O)N(R⁷)₂, C(O)NH₂, C(O)NHR⁷,C(O)N(R⁷)₂, C(O)NHOH, C(O)NHOR⁷, C(O)NHSO₂R⁷, C(O)NR⁷SO₂R⁷, SO₂NH₂,SO₂NHR⁷, SO₂N(R⁷)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR⁷, C(N)N(R⁷)₂, CNOH,CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; R⁵, at each occurrence,is independently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR⁵ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR⁸, OR⁸, SR⁸, S(O)R⁸, SO₂R⁸, NHR⁸, N(R⁸)₂, C(O)R⁸, C(O)NH₂, C(O)NHR⁸,C(O)N(R⁸)₂, NHC(O)R⁸, NR⁸C(O)R⁸, NHSO₂R⁸, NHC(O)OR⁸, SO₂NH₂, SO₂NHR⁸,SO₂N(R⁸)₂, NHC(O)NH₂, NHC(O)NHR⁸, OH, (O), C(O)OH, N₃, CN, NH₂, F, Cl,Br and I; R⁶, at each occurrence, is independently selected from thegroup consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl,cycloalkyl, and cycloalkenyl; wherein each R⁶ alkyl, alkenyl, andalkynyl is optionally substituted with one or more substituentsindependently selected from the group consisting of R⁹, OR⁹, SR⁹,S(O)R⁹, SO₂R⁹, NHR⁹, N(R⁹)₂, C(O)R⁹, C(O)NH₂, C(O)NHR⁹, C(O)N(R⁹)₂,NHC(O)R⁹, NR⁹C(O)R⁹, NHSO₂R⁹, NHC(O)OR⁹, SO₂NH₂, SO₂NHR⁹, SO₂N(R⁹)₂,NHC(O)NH₂, NHC(O)NHR⁹, OH, (O), C(O)OH, N₃, CN, NH₂, CF₃, CF₂CF₃, F, Cl,Br and I; R⁷, at each occurrence, is independently selected from thegroup consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl,cycloalkyl, and cycloalkenyl; R⁸, at each occurrence, is independentlyselected from the group consisting of alkyl, alkenyl, alkynyl, aryl,heterocyclyl, cycloalkyl, and cycloalkenyl; R⁹, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein thecyclic moieties represented by R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ areindependently optionally substituted with one or more substituentsindependently selected from the group consisting of R¹⁰, OR¹⁰, SR¹⁰,S(O)R¹⁰, C(O)C(O)R¹⁰, SO₂R¹⁰, C(O)R¹⁰, CO(O)R¹⁰, OC(O)R¹⁰, OC(O)OR¹⁰,NH₂, NHR¹⁰, N(R¹⁰)₂, NHC(O)R¹⁰, NR¹⁰C(O)R¹⁰, NHS(O)₂R¹⁰, NR¹⁰S(O)₂R¹⁰,NHC(O)OR¹⁰, NR¹⁰C(O)OR¹⁰, NHC(O)NH₂, NHC(O)NHR¹⁰, NHC(O)N(R¹⁰)₂,NR¹⁰C(O)NHR¹⁰, NR¹⁰C(O)N(R¹⁰)₂, C(O)NH₂, C(O)NHR¹⁰, C(O)N(R¹⁰)₂,C(O)NHOH, C(O)NHOR¹⁰, C(O)NHSO₂R¹⁰, C(O)NR¹⁰SO₂R¹⁰, SO₂NH₂, SO₂NHR¹⁰,SO₂N(R¹⁰)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹⁰, C(N)N(R¹⁰)₂, CNOH,CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I; R¹⁰, at each occurrence, isindependently selected from the group consisting of alkyl, alkenyl,alkynyl, aryl, heterocyclyl, cycloalkyl, and cycloalkenyl; wherein eachR¹⁰ alkyl, alkenyl, and alkynyl is optionally substituted with one ormore substituents independently selected from the group consisting ofR¹¹, OR¹¹, SR¹¹, S(O)R¹¹, SO₂R¹¹, C(O)R¹¹, CO(O)R¹¹, OC(O)R¹¹,OC(O)OR¹¹, NH₂, NHR¹¹, N(R¹¹)₂, NHC(O)R¹¹, NR¹¹C(O)R¹¹, NHS(O)₂R¹¹,NR¹¹S(O)₂R¹¹, NHC(O)OR¹¹, NR¹¹C(O)OR¹¹, NHC(O)NH₂, NHC(O)NHR¹¹,NHC(O)N(R¹¹)₂, NR¹¹C(O)NHR¹¹, NR¹¹C(O)N(R¹¹)₂, C(O)NH₂, C(O)NHR¹¹,C(O)N(R¹¹)₂, C(O)NHOH, C(O)NHOR¹¹, C(O)NHSO₂R¹¹, C(O)NR¹¹SO₂R¹¹, SO₂NH₂,SO₂NHR¹¹, SO₂N(R¹¹)₂, C(O)H, C(O)OH, C(N)NH₂, C(N)NHR¹¹, C(N)N(R¹¹)₂,CNOH, CNOCH₃, OH, (O), CN, N₃, NO₂, F, Cl, Br and I; wherein eachR¹⁰aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of R¹², OR¹², SR¹², S(O)R¹², SO₂R¹², C(O)R¹²,CO(O)R¹², OC(O)R¹², OC(O)OR¹², NH₂, NHR¹², N(R¹²)₂, NHC(O)R¹²,NR¹²C(O)R¹², NHS(O)₂R¹², NR¹²S(O)₂R¹², NHC(O)OR¹², NR¹²C(O)OR¹²,NHC(O)NH₂, NHC(O)NHR¹², NHC(O)N(R¹²)₂, NR¹²C(O)NHR¹², NR¹²C(O)N(R¹²)₂,C(O)NH₂, C(O)NHR¹², C(O)N(R¹²)₂, C(O)NHOH, C(O)NHOR¹², C(O)NHSO₂R′¹²,C(O)NR¹²SO₂R¹², SO₂NH₂, SO₂NHR¹², SO₂N(R¹²)₂, C(O)H, C(O)OH, C(N)NH₂,C(N)NHR¹², C(N)N(R¹²)₂, CNOH, CNOCH₃, OH, CN, N₃, NO₂, F, Cl, Br and I;R¹¹, at each occurrence, is independently selected from the groupconsisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl,and cycloalkenyl; wherein each R¹¹ alkyl, alkenyl, and alkynyl isoptionally substituted with alkyl or alkoxy; wherein each R¹¹ aryl,heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substitutedwith alkyl or alkoxy; and R¹², at each occurrence, is independentlyselected alkyl.
 2. The compound of claim 1, or a therapeuticallyacceptable salt thereof, wherein X¹ is CR¹ and X² is CR¹.
 3. Thecompound of claim 1 or claim 2, or a therapeutically acceptable saltthereof, wherein R¹, at each occurrence, is hydrogen.
 4. The compound ofclaim 1, or a therapeutically acceptable salt thereof, wherein R² isphenyl; wherein each R² phenyl is substituted with OR⁴.
 5. The compoundof claim 1, or a therapeutically acceptable salt thereof, wherein R² isphenyl; wherein each R² phenyl is substituted with R⁴.
 6. The compoundof claim 4 or 5, or a therapeutically acceptable salt thereof, whereinR⁴ is independently heterocyclyl.
 7. The compound of claim 1, selectedfrom the group consisting ofN-[4-({1-[(2S)-2-methylbutanoyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;3-(5-fluoropyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(6-methylpyridin-3-yl)-N-(4-{[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{1-[(2S)-2-methylbutanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)azetidine-1-carboxamide;N-{4-[1-(2-hydroxy-2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;methyl 4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)benzoate;N-(4-cyanophenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide; tert-butyl4-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)butyl]piperidine-1-carboxylate;N-{4-[1-(2,2-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3,3-dimethylbutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(methoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(methylsulfanyl)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(ethoxyacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2-methoxyethoxy)acetyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[3-(methylsulfanyl)propanoyl]-1,2,3,6-tetrahydropyridin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopropylcarbonyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopropylacetyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylpropanoyl)-1,2,3,6-tetrahydropyridin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;N-(4-{[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]oxy}phenyl)azetidine-1-carboxamide;N-[4-({1-[(1-acetylpiperidin-4-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[3-(morpholin-4-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[3-(4-methylpiperazin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({1-[3-(pyrrolidin-1-yl)propanoyl]piperidin-4-yl}oxy)phenyl]azetidine-1-carboxamide;N-(4-{[1-(cyclopropylacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(3-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(4-methylpentanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-butanoylpiperidin-4-yl)oxyl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(ethoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(cyclopropylcarbonyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(methoxyacetyl)piperidin-4-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[(tetrahydrofuran-3-ylmethyl)carbamoyl]phenyl}azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;tert-butyl3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]pyrrolidine-1-carboxylate;tert-butyl(3R)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;tert-butyl(3S)-3-[4-({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]pyrrolidine-1-carboxylate;tert-butyl3-[4({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]azetidine-1-carboxylate;tert-butyl3-[4({[3-(pyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenoxy]azetidine-1-carboxylate;3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl}phenyl]azetidine-1-carboxamide;N-{4-[1-(2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopropylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-benzoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4[-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopropylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-butanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({(3R)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydro-2H-pyran-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[(3S)-1-(2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;3-(pyridin-3-yl)-N-[4-({(3S)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]pyrrolidin-3-yl}oxy)phenyl]azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3S)-1-(tetrahydrofuran-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[(3S)-1-(cyclopropylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3S)-1-(2-hydroxy-2-methylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3S)-1-benzoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3S)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[(3S)-1-(cyclopropylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3S)-1-[(2S)-2-methylbutanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3S)-1-butanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydro-2H-pyran-4-ylacetyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopropylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-hydroxy-2-methylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-benzoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopropylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2S)-2-methylbutanoyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-butanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;tert-butyl4-[4-({[3-(2-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;tert-butyl4-[4-({[3-(4-chloropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;N-(4-{[1-(cyclopropylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(furan-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;tert-butyl4-[4-({[3-(2-fluoropyridin-3-yl)azetidin-1-yl]carbonyl}amino)phenyl]piperidine-1-carboxylate;N-{4-[(1-pentanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(ethoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(methoxyacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(3-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(4-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[1-(2-methylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2,2-dimethylpropanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[(1-butanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[(1-propanoylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2,2-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(3-methylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(3,3-dimethylbutanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(3,3,3-trifluoropropanoyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-[4-({1-[(1-methylcyclopropyl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2-methylpentanoyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[(1-acetylazetidin-3-yl)oxy]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(cyclohexylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(cyclopropylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(thiophen-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[1-(cyclopentylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(morpholin-4-ylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-[4-({1-[(3,5-dimethyl-1,2-oxazol-4-yl)carbonyl]azetidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[1-(1,2-oxazol-5-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(4-methylpiperazin-1-yl)acetyl]azetidin-3-yl]oxy)phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(N,N-dimethyl-beta-alanyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(furan-3-ylcarbonyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(1-methylcyclohexyl)carbonyl]azetidin-3-yl]oxy)phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(cyclopentylacetyl)azetidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[1-(pyrrolidin-1-ylacetyl)azetidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;3-(2-fluoropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(2-methylpropyl)-1H-pyrazol-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-propyl-1H-pyrazol-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;3-(4-chloropyridin-3-yl)-N-(4-{1-[(3S)-tetrahydrofuran-3-ylcarbonyl]piperidin-4-yl}phenyl)azetidine-1-carboxamide;3-(2-chloropyridin-3-yl)-N-{4-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-[4-(1-pentanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(4-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-methylpentanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-ethoxypropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[143,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-butanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(ethoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-methylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(N-acetyl-L-leucyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2-methoxyethoxy)acetyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopentylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(1-methylcyclohexyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(furan-3-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-acetylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(methoxyacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(morpholin-4-ylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(furan-2-ylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[1-methyl-1H-pyrrol-2-yl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-propanoylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopentylacetyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-pentanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(4-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-methylpentanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-ethoxypropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1(3,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylpropanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(ethoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-methylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(N-acetyl-L-leucyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2-methoxyethoxy)acetyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopentylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[1-methylcyclohexyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(furan-3-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-acetylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(methoxyacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(morpholin-4-ylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)azetidin-3--yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(furan-2-ylcarbonyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[1-methyl-1H-pyrrol-2-yl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-propanoylazetidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[1-methylcyclopropyl)carbonyl]azetidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(cyclopentylacetyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1(2,3-dimethylbutanoyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopentylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylmethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1(3,3-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylpentyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;-{4-[1-(3-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-ethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylpropyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-butylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-propylpiperidin-4-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-cyclopropylethyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylbutyl)piperidin-4-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopentylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[3,3-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopropylmethyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylpentyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-2-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(2-methylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-ethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylpropyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(tetrahydrofuran-3-ylmethyl)azetidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylbutyl)azetidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-pentanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(1S,4R)-bicyclo[2.2.1]hept-2-ylacetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopentylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;N-{4-[1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(5-oxo-L-prolyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-ethoxypropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(4-methylpentanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-acetylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-propanoylpyrrolidin-3-yl)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-{4-[1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(ethoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[3,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-oxopropanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(methoxyacetyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclohexylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3-methylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopentylcarbonyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-pentanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(3-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(bicyclo[2.2.1]hept-2-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(cyclopentylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(2-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(morpholin-4-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(furan-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(pyrrolidin-1-ylacetyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(5-oxo-D-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(N,N-dimethyl-beta-alanyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(1,3-thiazol-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-3-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(1-methylcyclopropyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(3-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(4,4,4-trifluorobutanoyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(4-methylpiperazin-1-yl)acetyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(5-oxo-L-prolyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(3-ethoxypropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(4-methylpentanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(1-methylcyclohexyl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(cyclohexylacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(N-acetyl-L-leucyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-propanoylpyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(2-methoxyethoxy)acetyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[3-(morpholin-4-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(2,2-dimethylpropanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[(5-methylthiophen-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;3-(pyridin-3-yl)-N-(4-{[(3R)-1-(thiophen-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)azetidine-1-carboxamide;N-[4-{(3R)-1-[(1-methyl-1H-pyrrol-2-yl)carbonyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(furan-2-ylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-({(3R)-1-[3-(piperidin-1-yl)propanoyl]pyrrolidin-3-yl}oxy)phenyl]-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(ethoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(3,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(2,2-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(methoxyacetyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(cyclohexylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(3-methylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(cyclopentylcarbonyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-(4-{[(3R)-1-(2,3-dimethylbutanoyl)pyrrolidin-3-yl]oxy}phenyl)-3-(pyridin-3-yl)azetidine-1-carboxamide;N-[4-(1-benzoylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-fluorobenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2-methylbenzoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[1-(2,2-dimethylpropanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopropylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-[4-(1-acetylpiperidin-4-yl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[1-(3,3-dimethylbutanoyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclobutylcarbonyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;3-(pyridazin-3-yl)-N-{4-[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;3-(pyridazin-3-yl)-N-{4-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]phenyl}azetidine-1-carboxamide;N-(4-{1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[1-(cyclopropylacetyl)piperidin-4-yl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[(1-benzoylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2-fluorobenzoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2,2-dimethylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(3,3-dimethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-(4-{[1-(2-ethylbutanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;3-(pyridazin-3-yl)-N-(4-{[1-(4,4,4-trifluorobutanoyl)piperidin-4-yl]methyl}phenyl)azetidine-1-carboxamide;N-(4-{[1-(2-methylpropanoyl)piperidin-4-yl]methyl}phenyl)-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-{4-[(1-acetylpiperidin-4-yl)methyl]phenyl}-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(2S)-2-methylbutanoyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;N-[4-({1-[(1-methylcyclopropyl)carbonyl]piperidin-4-yl}methyl)phenyl]-3-(pyridazin-3-yl)azetidine-1-carboxamide;and pharmaceutically acceptable salts thereof.
 8. A compositioncomprising an excipient and a therapeutically effective amount of acompound of claim 1, or pharmaceutically acceptable salts thereof.